Table of SynGAP1 Isoform α2 (UniProt Q96PV0-1) Missense Variants.

c.dna	Variant	SGM Consensus	Domain	IUPred2		ANCHOR2		AlphaFold		MobiDB	ClinVar			gnomAD			ESM1b		AlphaMissense			REVEL		PSMutPred			FoldX			Rosetta		Foldetta		PremPS		PROVEAN		PolyPhen-2 HumDiv		PolyPhen-2 HumVar		FATHMM		SIFT				PAM		Physical		SASA		Normalized B-factor backbone		Normalized B-factor sidechain		SynGAP Structural Annotation									DOI
				Score	Prediction	Score	Prediction	pLDDT	disorder	disorder	Clinical Status	Review	Subm.	ID	Allele count	Allele freq.	LLR score	Prediction	Pathogenicity	Class	Optimized	Score	Prediction	IP RF	SP RF	Prediction	Average ΔΔG	Prediction	StdDev	ΔΔG	Prediction	ΔΔG	Prediction	ΔΔG	Prediction	Score	Prediction	pph2_prob	Prediction	pph2_prob	Prediction	Nervous System Score	Prediction	Prediction	Status	Conservation	Sequences	PAM250	PAM120	Hydropathy Δ	MW Δ	Average	Δ	Δ	StdDev	Δ	StdDev	Secondary	Tertiary bonds	Inside out	GAP-Ras interface	At membrane	No effect	MD Alert	Verdict	Description
c.695C>T	A232V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A232V is catalogued in gnomAD (ID 6‑33435546‑C‑T) but has no ClinVar entry. Functional prediction tools show mixed results: benign calls come from FoldX, Rosetta, Foldetta, polyPhen‑2 HumVar, SIFT, and FATHMM, whereas pathogenic calls are reported by REVEL, PROVEAN, polyPhen‑2 HumDiv, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic, and the Foldetta stability assessment predicts benign. premPS is inconclusive and therefore not considered. Overall, the majority of independent predictors lean toward pathogenicity, but the stability‑based Foldetta suggests a benign effect. With no ClinVar classification to contradict, the variant is most likely pathogenic according to the prevailing computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.254060	Structured	0.307228	Uncertain	0.878	0.305	0.000				6-33435546-C-T	2	1.24e-6	-9.418	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	0.539	Likely Pathogenic	0.1202	0.6027		0.40	Likely Benign	0.1	0.23	Likely Benign	0.32	Likely Benign	0.55	Ambiguous	-2.99	Deleterious	0.608	Possibly Damaging	0.240	Benign	5.85	Benign	0.06	Tolerated	3.40	14	0	0	2.4	28.05
c.3329G>T	S1110I 2D AIThe SynGAP1 missense variant S1110I is catalogued in gnomAD (ID 6‑33443881‑G‑T) but has no ClinVar submission. Functional prediction tools show a split: six algorithms (REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a benign effect, whereas three (PROVEAN, SIFT, FATHMM) predict pathogenicity. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized classifies the variant as benign; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign, two pathogenic); Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, has no available result for this residue. Overall, the preponderance of evidence points to a benign impact, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.912647	Disordered	0.934156	Binding	0.346	0.892	0.875				6-33443881-G-T			-6.124	Likely Benign	0.198	Likely Benign	Likely Benign	0.038	Likely Benign	0.1203	0.4971											-2.99	Deleterious	0.007	Benign	0.003	Benign	2.17	Pathogenic	0.01	Affected	4.32	2	-2	-1	5.3	26.08
c.1499T>G	L500R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L500R is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as pathogenic include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool predicts a benign effect; the benign group is empty. Predictions that are uncertain or inconclusive are Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Based on the overwhelming agreement among pathogenic predictors and the lack of any benign calls, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status (which has no entry). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.066181	Structured	0.382942	Uncertain	0.893	0.150	0.000							-15.576	Likely Pathogenic	0.789	Likely Pathogenic	Ambiguous	0.794	Likely Pathogenic	0.1204	0.0488		2.23	Destabilizing	0.1	1.04	Ambiguous	1.64	Ambiguous	1.11	Destabilizing	-5.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.02	Pathogenic	0.03	Affected			-3	-2	-8.3	43.03
c.2075T>G	L692R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L692R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic outcome; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. No prediction or folding stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.064632	Structured	0.295225	Uncertain	0.966	0.243	0.000							-16.656	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.611	Likely Pathogenic	0.1204	0.0488		4.34	Destabilizing	0.0	5.51	Destabilizing	4.93	Destabilizing	1.96	Destabilizing	-5.98	Deleterious	0.999	Probably Damaging	0.895	Possibly Damaging	3.07	Benign	0.00	Affected			-3	-2	-8.3	43.03
c.2591C>A	A864E 2D AIThe SynGAP1 missense variant A864E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors a benign outcome. Foldetta, which evaluates protein‑folding stability, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing clinical database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.549308	Disordered	0.611966	Binding	0.269	0.788	0.250							-5.508	Likely Benign	0.350	Ambiguous	Likely Benign	0.153	Likely Benign	0.1204	0.2037											0.10	Neutral	0.138	Benign	0.070	Benign	2.45	Pathogenic	0.04	Affected			0	-1	-5.3	58.04
c.2738C>A	T913K 2D AIThe SynGAP1 missense variant T913K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for T913K, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.763517	Binding	0.339	0.899	0.375							-4.145	Likely Benign	0.619	Likely Pathogenic	Likely Benign	0.152	Likely Benign	0.1204	0.3491											-1.46	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.70	Benign	0.05	Affected			0	-1	-3.2	27.07
c.3722T>G	L1241R 2D AIThe SynGAP1 missense variant L1241R is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign outcome, whereas the remaining predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic status. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus confirms a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools indicates that the variant is most likely pathogenic, and this conclusion is consistent with the absence of any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.545602	Disordered	0.488880	Uncertain	0.828	0.541	0.375							-14.178	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	0.366	Likely Benign	0.1204	0.0488											-4.69	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.62	Pathogenic	0.00	Affected			-3	-2	-8.3	43.03
c.1221G>C	Q407H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q407H (C2 domain) has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict pathogenicity: premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, is uncertain. No evidence from FoldX, Rosetta, or Foldetta supports a benign outcome. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.109221	Structured	0.382522	Uncertain	0.916	0.271	0.000							-10.526	Likely Pathogenic	0.830	Likely Pathogenic	Ambiguous	0.206	Likely Benign	0.1205	0.3154		0.59	Ambiguous	0.0	0.61	Ambiguous	0.60	Ambiguous	1.10	Destabilizing	-4.51	Deleterious	0.982	Probably Damaging	0.947	Probably Damaging	3.88	Benign	0.01	Affected	3.38	28	0	3	0.3	9.01
c.1221G>T	Q407H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q407H is listed in ClinVar with an uncertain significance (ClinVar ID 2772184.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and FATHMM, while pathogenic predictions are made by premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Predictions marked as uncertain include FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for Q407H. This conclusion does not conflict with the ClinVar designation of uncertain significance, which remains unresolved pending further evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.109221	Structured	0.382522	Uncertain	0.916	0.271	0.000	Uncertain		1				-10.526	Likely Pathogenic	0.830	Likely Pathogenic	Ambiguous	0.206	Likely Benign	0.1205	0.3154		0.59	Ambiguous	0.0	0.61	Ambiguous	0.60	Ambiguous	1.10	Destabilizing	-4.51	Deleterious	0.982	Probably Damaging	0.947	Probably Damaging	3.88	Benign	0.01	Affected	3.38	28	0	3	0.3	9.01
c.1223C>A	T408K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T408K is not listed in ClinVar (ClinVar ID None) and has no reported allele in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, SIFT, FATHMM, polyPhen‑2 HumVar, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default; premPS remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labeling it likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicting a benign effect. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.161087	Structured	0.370935	Uncertain	0.907	0.239	0.000							-11.841	Likely Pathogenic	0.756	Likely Pathogenic	Likely Benign	0.131	Likely Benign	0.1205	0.3384		-0.44	Likely Benign	0.2	0.14	Likely Benign	-0.15	Likely Benign	0.88	Ambiguous	-3.79	Deleterious	0.851	Possibly Damaging	0.163	Benign	4.17	Benign	0.15	Tolerated			0	-1	-3.2	27.07
c.1441C>A	H481N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 H481N missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. Two tools—Rosetta and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign based on current predictive data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.257454	Structured	0.430977	Uncertain	0.764	0.247	0.000							-8.229	Likely Pathogenic	0.381	Ambiguous	Likely Benign	0.205	Likely Benign	0.1205	0.1631		0.16	Likely Benign	0.1	0.54	Ambiguous	0.35	Likely Benign	0.09	Likely Benign	-4.11	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.68	Benign	0.57	Tolerated			2	1	-0.3	-23.04
c.1498C>G	L500V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L500V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on benign effect include SIFT and AlphaMissense‑Optimized, whereas a majority of tools predict pathogenicity: SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Predictions that are inconclusive are FoldX, Rosetta, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence from multiple independent predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.066181	Structured	0.382942	Uncertain	0.893	0.150	0.000							-12.963	Likely Pathogenic	0.379	Ambiguous	Likely Benign	0.565	Likely Pathogenic	0.1205	0.1860		1.92	Ambiguous	0.0	0.81	Ambiguous	1.37	Ambiguous	1.11	Destabilizing	-2.98	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	-1.24	Pathogenic	0.11	Tolerated			2	1	0.4	-14.03
c.2555G>T	G852V 2D AIThe SynGAP1 missense variant G852V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for G852V, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.733139	Disordered	0.506063	Binding	0.276	0.816	0.625							-5.629	Likely Benign	0.085	Likely Benign	Likely Benign	0.125	Likely Benign	0.1205	0.4173											-1.30	Neutral	0.918	Possibly Damaging	0.697	Possibly Damaging	4.19	Benign	0.02	Affected			-1	-3	4.6	42.08
c.3457C>T	R1153W 2D AIThe SynGAP1 missense variant R1153W is listed in ClinVar (ID 521099.0) with an uncertain significance designation and is present in the gnomAD database (variant ID 6‑33444492‑C‑T). Functional prediction tools cluster into two groups: benign predictions from REVEL and ESM1b, and pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus method SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as likely pathogenic. AlphaMissense‑Optimized independently predicts pathogenicity. No Foldetta stability assessment is available for this residue. Taken together, the majority of evidence points to a pathogenic effect, which is in contrast to the ClinVar uncertain classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.762850	Disordered	0.820118	Binding	0.361	0.848	0.625	Uncertain		2	6-33444492-C-T	2	1.24e-6	-5.812	Likely Benign	0.994	Likely Pathogenic	Likely Pathogenic	0.317	Likely Benign	0.1205	0.3340											-5.88	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.46	Pathogenic	0.00	Affected	3.77	5	2	-3	3.6	30.03
c.1904A>C	N635T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N635T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, SIFT, and ESM1b; polyPhen‑2 HumVar, however, classifies it as benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain, and FoldX and premPS also yield uncertain results. Overall, the majority of evidence (five benign vs. four pathogenic) supports a benign classification. This conclusion is consistent with the lack of ClinVar annotation and gnomAD presence, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.039760	Structured	0.060246	Uncertain	0.900	0.252	0.000							-11.705	Likely Pathogenic	0.256	Likely Benign	Likely Benign	0.240	Likely Benign	0.1206	0.4032		1.50	Ambiguous	0.1	0.44	Likely Benign	0.97	Ambiguous	0.81	Ambiguous	-5.58	Deleterious	0.536	Possibly Damaging	0.184	Benign	2.98	Benign	0.04	Affected			0	0	2.8	-13.00
c.2572A>T	S858C 2D AIThe SynGAP1 missense variant S858C is reported in ClinVar as “Not submitted” and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of computational evidence points to a benign effect, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.482724	Uncertain	0.305	0.833	0.375							-6.767	Likely Benign	0.108	Likely Benign	Likely Benign	0.139	Likely Benign	0.1206	0.6155											-1.93	Neutral	0.940	Possibly Damaging	0.979	Probably Damaging	4.06	Benign	0.02	Affected			0	-1	3.3	16.06
c.1517T>G	L506R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L506R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Pathogenic. Thus, all available evidence indicates that the variant is most likely pathogenic, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.034884	Structured	0.279180	Uncertain	0.924	0.196	0.000							-14.119	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	0.738	Likely Pathogenic	0.1207	0.0488		4.92	Destabilizing	0.6	5.85	Destabilizing	5.39	Destabilizing	1.77	Destabilizing	-5.97	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.54	Pathogenic	0.00	Affected			-3	-2	-8.3	43.03
c.661G>C	E221Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E221Q missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Two tools predict a pathogenic outcome: ESM1b and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two pathogenic vs two benign), and Foldetta predicts a benign effect. Overall, the majority of evidence (10 benign vs 2 pathogenic) supports a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.127496	Structured	0.413334	Uncertain	0.891	0.283	0.000							-8.243	Likely Pathogenic	0.825	Likely Pathogenic	Ambiguous	0.455	Likely Benign	0.1207	0.7690		-0.26	Likely Benign	0.1	-0.33	Likely Benign	-0.30	Likely Benign	0.12	Likely Benign	-1.64	Neutral	0.028	Benign	0.015	Benign	6.13	Benign	0.23	Tolerated			2	2	0.0	-0.98
c.1809G>A	M603I 2D AIThe SynGAP1 missense variant M603I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include Rosetta, Foldetta, and premPS, whereas the majority of tools predict it to be pathogenic: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX reports an uncertain effect. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the balance of evidence points to a pathogenic effect for M603I, and this conclusion does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.011342	Structured	0.197847	Uncertain	0.942	0.176	0.000							-10.086	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	0.699	Likely Pathogenic	0.1208	0.2350		0.81	Ambiguous	0.6	0.07	Likely Benign	0.44	Likely Benign	-0.07	Likely Benign	-3.32	Deleterious	0.833	Possibly Damaging	0.886	Possibly Damaging	-1.21	Pathogenic	0.03	Affected			2	1	2.6	-18.03
c.1809G>C	M603I 2D AIThe SynGAP1 missense variant M603I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include Rosetta, Foldetta, and premPS, whereas the majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX reports an uncertain result. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the preponderance of evidence points to a pathogenic effect for M603I. This conclusion is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.011342	Structured	0.197847	Uncertain	0.942	0.176	0.000							-10.086	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	0.699	Likely Pathogenic	0.1208	0.2350		0.81	Ambiguous	0.6	0.07	Likely Benign	0.44	Likely Benign	-0.07	Likely Benign	-3.32	Deleterious	0.833	Possibly Damaging	0.886	Possibly Damaging	-1.21	Pathogenic	0.03	Affected			2	1	2.6	-18.03
c.1809G>T	M603I 2D AIThe SynGAP1 missense variant M603I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include Rosetta, Foldetta, and premPS, whereas the majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX reports an uncertain result. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the preponderance of evidence points to a pathogenic effect for M603I. This conclusion is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.011342	Structured	0.197847	Uncertain	0.942	0.176	0.000							-10.086	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	0.698	Likely Pathogenic	0.1208	0.2350		0.81	Ambiguous	0.6	0.07	Likely Benign	0.44	Likely Benign	-0.07	Likely Benign	-3.32	Deleterious	0.833	Possibly Damaging	0.886	Possibly Damaging	-1.21	Pathogenic	0.03	Affected			2	1	2.6	-18.03
c.2066T>G	L689R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L689R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (both HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate pathogenicity, whereas only FATHMM predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, is pathogenic. No predictions are missing or inconclusive. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.042364	Structured	0.227227	Uncertain	0.963	0.248	0.000							-17.776	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.609	Likely Pathogenic	0.1208	0.0530		5.91	Destabilizing	0.6	5.61	Destabilizing	5.76	Destabilizing	2.14	Destabilizing	-5.98	Deleterious	1.000	Probably Damaging	0.932	Probably Damaging	3.15	Benign	0.00	Affected			-3	-2	-8.3	43.03
c.2630T>A	L877Q 2D AIThe SynGAP1 missense variant L877Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT uniformly predict a pathogenic impact. AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, SGM‑Consensus is Likely Benign, and Foldetta (which integrates FoldX‑MD and Rosetta outputs) is not available for this variant. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.653063	Disordered	0.634010	Binding	0.265	0.875	0.250							-5.919	Likely Benign	0.460	Ambiguous	Likely Benign	0.152	Likely Benign	0.1208	0.0919											-1.58	Neutral	0.986	Probably Damaging	0.876	Possibly Damaging	2.57	Benign	0.03	Affected			-2	-2	-7.3	14.97
c.1655G>T	C552F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C552F is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include Rosetta, premPS, and SIFT, whereas the majority of tools predict it to be pathogenic: REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score. FoldX and Foldetta give uncertain results. High‑accuracy methods specifically report AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the consensus of the available predictions indicates that the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.013265	Structured	0.005714	Uncertain	0.955	0.256	0.000							-14.979	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	0.759	Likely Pathogenic	0.1209	0.3081		-1.01	Ambiguous	0.1	-0.35	Likely Benign	-0.68	Ambiguous	0.40	Likely Benign	-9.51	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.25	Pathogenic	0.07	Tolerated			-4	-2	0.3	44.04
c.1763T>G	L588R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L588R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity uniformly classify the variant as pathogenic: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy methods corroborate this: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. All available evidence points to a deleterious impact. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.038042	Structured	0.082229	Uncertain	0.887	0.214	0.000							-15.602	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.942	Likely Pathogenic	0.1209	0.0530		6.96	Destabilizing	0.4	6.14	Destabilizing	6.55	Destabilizing	2.07	Destabilizing	-5.98	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.42	Pathogenic	0.00	Affected			-3	-2	-8.3	43.03
c.2056G>T	G686C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G686C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from FoldX, Rosetta, FATHMM, and the protein‑folding stability method Foldetta; pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized, with the SGM‑Consensus score labeling the variant as Likely Pathogenic. High‑accuracy assessments further show AlphaMissense‑Optimized as Pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.109221	Structured	0.177104	Uncertain	0.919	0.268	0.000							-12.790	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.553	Likely Pathogenic	0.1209	0.3246		0.25	Likely Benign	0.2	0.41	Likely Benign	0.33	Likely Benign	0.93	Ambiguous	-8.14	Deleterious	1.000	Probably Damaging	0.988	Probably Damaging	3.31	Benign	0.02	Affected			-3	-3	2.9	46.09
c.2221C>A	P741T 2D AIThe SynGAP1 missense variant P741T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.885302	Disordered	0.493550	Uncertain	0.354	0.859	0.875							-4.626	Likely Benign	0.061	Likely Benign	Likely Benign	0.077	Likely Benign	0.1209	0.5080											-0.54	Neutral	0.010	Benign	0.022	Benign	2.86	Benign	0.05	Affected			0	-1	0.9	3.99
c.2099T>G	L700R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L700R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: benign calls come from REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic calls are made by Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels the variant as Likely Pathogenic. High‑accuracy assessments are mixed: AlphaMissense‑Optimized is inconclusive, SGM Consensus remains Likely Pathogenic, and Foldetta predicts a destabilizing, pathogenic effect. Overall, the preponderance of evidence points to a pathogenic impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.113710	Structured	0.416255	Uncertain	0.927	0.331	0.000							-12.389	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	0.485	Likely Benign	0.1210	0.0488		1.82	Ambiguous	0.1	4.19	Destabilizing	3.01	Destabilizing	1.89	Destabilizing	-4.29	Deleterious	0.728	Possibly Damaging	0.249	Benign	3.35	Benign	0.01	Affected			-3	-2	-8.3	43.03
c.2974G>C	V992L 2D AIThe SynGAP1 missense variant V992L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the evidence strongly supports a benign classification, and this conclusion is consistent with the lack of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.921728	Binding	0.331	0.917	0.750							-2.333	Likely Benign	0.086	Likely Benign	Likely Benign	0.060	Likely Benign	0.1211	0.5202											-0.50	Neutral	0.086	Benign	0.038	Benign	4.24	Benign	0.16	Tolerated			2	1	-0.4	14.03
c.3063G>C	Q1021H 2D AIThe SynGAP1 missense variant Q1021H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar, as no ClinVar status is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.899122	Disordered	0.979641	Binding	0.326	0.763	0.500							-4.694	Likely Benign	0.664	Likely Pathogenic	Likely Benign	0.184	Likely Benign	0.1211	0.3601											-1.72	Neutral	0.996	Probably Damaging	0.995	Probably Damaging	2.61	Benign	0.01	Affected			3	0	0.3	9.01
c.3063G>T	Q1021H 2D AIThe SynGAP1 missense variant Q1021H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.899122	Disordered	0.979641	Binding	0.326	0.763	0.500							-4.694	Likely Benign	0.664	Likely Pathogenic	Likely Benign	0.184	Likely Benign	0.1211	0.3601											-1.72	Neutral	0.996	Probably Damaging	0.995	Probably Damaging	2.61	Benign	0.01	Affected			3	0	0.3	9.01
c.2002T>A	S668T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S668T is not reported in ClinVar (ClinVar ID: None) and has no entries in gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, premPS, FATHMM, AlphaMissense‑Optimized, and polyPhen2_HumVar. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen2_HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome; Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result. No evidence from FoldX or Rosetta alone is conclusive. Overall, the balance of predictions leans toward pathogenicity, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.247041	Structured	0.084935	Uncertain	0.922	0.370	0.000							-11.860	Likely Pathogenic	0.703	Likely Pathogenic	Likely Benign	0.238	Likely Benign	0.1212	0.5918		1.73	Ambiguous	0.7	0.89	Ambiguous	1.31	Ambiguous	0.27	Likely Benign	-2.99	Deleterious	0.844	Possibly Damaging	0.198	Benign	3.24	Benign	0.02	Affected			1	1	0.1	14.03
c.3550T>A	S1184T 2D AIThe SynGAP1 missense variant S1184T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote) is also benign. Foldetta results are not available, so they do not influence the assessment. Overall, the preponderance of evidence from multiple prediction algorithms and consensus methods indicates that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.648219	Disordered	0.514669	Binding	0.624	0.642	0.500							-4.250	Likely Benign	0.712	Likely Pathogenic	Likely Benign	0.085	Likely Benign	0.1212	0.5004											-1.27	Neutral	0.979	Probably Damaging	0.973	Probably Damaging	2.70	Benign	0.18	Tolerated			1	1	0.1	14.03
c.2953A>C	S985R 2D AIThe SynGAP1 missense variant S985R has no ClinVar entry and is not reported in gnomAD. Prediction tools that classify it as benign include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Those that predict pathogenicity are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus remains benign; Foldetta, a protein‑folding stability method, has no available result for this variant. Consequently, the evidence is split evenly between benign and pathogenic predictions, with no contradiction to ClinVar status. The variant’s impact remains uncertain, and no definitive benign or pathogenic classification can be assigned based solely on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.720929	Disordered	0.941547	Binding	0.302	0.896	0.750							-6.148	Likely Benign	0.991	Likely Pathogenic	Likely Pathogenic	0.174	Likely Benign	0.1213	0.3905											-2.40	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	2.52	Benign	0.00	Affected			0	-1	-3.7	69.11
c.2955T>A	S985R 2D AIThe SynGAP1 missense variant S985R has no ClinVar entry and is not reported in gnomAD. Consensus predictions from multiple in‑silico tools are split: benign calls come from REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) which reports a likely benign outcome. Pathogenic calls arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments are mixed: AlphaMissense‑Optimized predicts pathogenic, whereas the SGM‑Consensus (a majority‑vote aggregator) predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the predictions are evenly divided, leaving the variant’s clinical significance uncertain; it does not contradict any ClinVar status because none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.720929	Disordered	0.941547	Binding	0.302	0.896	0.750							-6.148	Likely Benign	0.991	Likely Pathogenic	Likely Pathogenic	0.203	Likely Benign	0.1213	0.3905											-2.40	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	2.52	Benign	0.00	Affected			0	-1	-3.7	69.11
c.2955T>G	S985R 2D AISynGAP1 missense variant S985R has no ClinVar record and is not present in gnomAD. Computational predictions are mixed: benign calls come from REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Pathogenic calls come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy tools give a split result: AlphaMissense‑Optimized predicts pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely benign; Foldetta data are unavailable. Consequently, the variant’s predicted impact is ambiguous, with an equal number of benign and pathogenic scores. No ClinVar evidence contradicts these predictions. Thus, the variant is best classified as of uncertain significance, with no clear bias toward benign or pathogenic status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.720929	Disordered	0.941547	Binding	0.302	0.896	0.750							-6.148	Likely Benign	0.991	Likely Pathogenic	Likely Pathogenic	0.203	Likely Benign	0.1213	0.3905											-2.40	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	2.52	Benign	0.00	Affected			0	-1	-3.7	69.11
c.3328A>T	S1110C 2D AIThe SynGAP1 missense variant S1110C is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also resolves to benign (2 benign vs. 1 pathogenic vote). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of evidence—including the high‑accuracy consensus—points to a benign impact. This conclusion is not contradicted by ClinVar, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.912647	Disordered	0.934156	Binding	0.346	0.892	0.875							-7.250	In-Between	0.096	Likely Benign	Likely Benign	0.027	Likely Benign	0.1214	0.5954											-2.12	Neutral	0.898	Possibly Damaging	0.477	Possibly Damaging	2.16	Pathogenic	0.01	Affected			0	-1	3.3	16.06
c.3633G>A	M1211I 2D AIThe SynGAP1 missense variant M1211I is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6-33446625-G-A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are AlphaMissense‑Default, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy predictions therefore point to a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus also indicates benign. Based on the aggregate predictions, the variant is most likely benign, which does not contradict the ClinVar “Uncertain” status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.585406	Disordered	0.578388	Binding	0.876	0.565	0.500	Uncertain		1	6-33446625-G-A	3	1.86e-6	-1.537	Likely Benign	0.764	Likely Pathogenic	Likely Benign	0.298	Likely Benign	0.1214	0.2839											-0.42	Neutral	0.969	Probably Damaging	0.968	Probably Damaging	5.40	Benign	1.00	Tolerated	3.77	5	1	2	2.6	-18.03
c.3633G>C	M1211I 2D AIThe SynGAP1 missense variant M1211I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.585406	Disordered	0.578388	Binding	0.876	0.565	0.500							-1.537	Likely Benign	0.764	Likely Pathogenic	Likely Benign	0.298	Likely Benign	0.1214	0.2839											-0.42	Neutral	0.969	Probably Damaging	0.968	Probably Damaging	5.40	Benign	1.00	Tolerated	3.77	5	1	2	2.6	-18.03
c.3633G>T	M1211I 2D AIThe SynGAP1 missense variant M1211I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely benign (three benign votes versus one pathogenic). High‑accuracy assessment by AlphaMissense‑Optimized confirms a benign prediction, whereas the Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a benign effect for M1211I, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.585406	Disordered	0.578388	Binding	0.876	0.565	0.500							-1.537	Likely Benign	0.764	Likely Pathogenic	Likely Benign	0.298	Likely Benign	0.1214	0.2839											-0.42	Neutral	0.969	Probably Damaging	0.968	Probably Damaging	5.40	Benign	1.00	Tolerated	3.77	5	1	2	2.6	-18.03
c.4025A>T	D1342V 2D AIThe SynGAP1 missense variant D1342V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign and the SGM‑Consensus also indicating a likely benign outcome; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.921076	Disordered	0.981682	Binding	0.316	0.678	0.875							-2.890	Likely Benign	0.317	Likely Benign	Likely Benign	0.089	Likely Benign	0.1214	0.5617											-1.27	Neutral	0.588	Possibly Damaging	0.212	Benign	4.01	Benign	0.00	Affected			-2	-3	7.7	-15.96
c.1901C>T	A634V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A634V is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools largely converge on a deleterious effect: pathogenic calls are made by REVEL, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score, while only FATHMM predicts a benign outcome; Rosetta remains inconclusive. High‑accuracy assessments reinforce the pathogenic trend: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is pathogenic. Taken together, the overwhelming majority of evidence supports a pathogenic effect for A634V, which is in contrast to its current ClinVar classification of uncertain significance. Therefore, the variant is most likely pathogenic, contradicting its ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.085092	Structured	0.052058	Uncertain	0.932	0.242	0.000	Uncertain		1				-12.612	Likely Pathogenic	0.971	Likely Pathogenic	Likely Pathogenic	0.631	Likely Pathogenic	0.1215	0.4371		2.67	Destabilizing	0.2	1.44	Ambiguous	2.06	Destabilizing	1.14	Destabilizing	-3.98	Deleterious	0.997	Probably Damaging	0.976	Probably Damaging	2.55	Benign	0.01	Affected			0	0	2.4	28.05
c.1947G>A	M649I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant M649I has no ClinVar entry and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas the majority of tools (SGM‑Consensus, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; Rosetta is inconclusive and is not counted. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Taken together, the preponderance of evidence supports a pathogenic classification for M649I, and this conclusion does not conflict with ClinVar status, which is currently unavailable. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.051831	Structured	0.360413	Uncertain	0.962	0.345	0.000							-9.361	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	0.449	Likely Benign	0.1215	0.2980		2.42	Destabilizing	0.2	1.96	Ambiguous	2.19	Destabilizing	1.01	Destabilizing	-3.99	Deleterious	0.672	Possibly Damaging	0.093	Benign	3.40	Benign	0.02	Affected	3.38	27	2	1	2.6	-18.03	243.7	21.5	0.0	0.1	0.0	0.1							X	Potentially Benign	The thioether side chain of Met649, located on an α helix (res. Ser641-Glu666), bridges Phe652, Phe648, and Phe639 in an inter-helix hydrophobic cavity in the WT simulations. In the variant simulations, the sec-butyl side chain of Ile649 maintains hydrophobic interactions with nearby residues, with no significant effects on the protein structure.However, methionine is known as a bridging motif for aromatic residues, and these Met-aromatic interactions are lost in the variant. Indeed, in the second variant simulation,the bridging of Phe652, Phe648 and Phe639 is completely lost. In reality, the effect could be more severe on the structure during the protein folding.
c.1947G>C	M649I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M649I is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas the majority of other in silico predictors (FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) report a pathogenic outcome; Rosetta is inconclusive. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. Overall, the preponderance of evidence points to a pathogenic effect for M649I, which is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.051831	Structured	0.360413	Uncertain	0.962	0.345	0.000	Uncertain		1				-9.361	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	0.449	Likely Benign	0.1215	0.2980		2.42	Destabilizing	0.2	1.96	Ambiguous	2.19	Destabilizing	1.01	Destabilizing	-3.99	Deleterious	0.672	Possibly Damaging	0.093	Benign	3.40	Benign	0.02	Affected	3.38	27	2	1	2.6	-18.03	243.7	21.5	0.0	0.1	0.0	0.1							X	Potentially Benign	The thioether side chain of Met649, located on an α helix (res. Ser641-Glu666), bridges Phe652, Phe648, and Phe639 in an inter-helix hydrophobic cavity in the WT simulations. In the variant simulations, the sec-butyl side chain of Ile649 maintains hydrophobic interactions with nearby residues, with no significant effects on the protein structure.However, methionine is known as a bridging motif for aromatic residues, and these Met-aromatic interactions are lost in the variant. Indeed, in the second variant simulation,the bridging of Phe652, Phe648 and Phe639 is completely lost. In reality, the effect could be more severe on the structure during the protein folding.
c.1947G>T	M649I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M649I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 HumVar, and FATHMM, whereas pathogenic calls are made by FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, votes strongly for pathogenicity (3/4 pathogenic). High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote) is likely pathogenic, and Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, also predicts pathogenic. Rosetta alone is uncertain and is treated as unavailable. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.051831	Structured	0.360413	Uncertain	0.962	0.345	0.000							-9.361	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	0.449	Likely Benign	0.1215	0.2980		2.42	Destabilizing	0.2	1.96	Ambiguous	2.19	Destabilizing	1.01	Destabilizing	-3.99	Deleterious	0.672	Possibly Damaging	0.093	Benign	3.40	Benign	0.02	Affected	3.38	27	2	1	2.6	-18.03	243.7	21.5	0.0	0.1	0.0	0.1							X	Potentially Benign	The thioether side chain of Met649, located on an α helix (res. Ser641-Glu666), bridges Phe652, Phe648, and Phe639 in an inter-helix hydrophobic cavity in the WT simulations. In the variant simulations, the sec-butyl side chain of Ile649 maintains hydrophobic interactions with nearby residues, with no significant effects on the protein structure.However, methionine is known as a bridging motif for aromatic residues, and these Met-aromatic interactions are lost in the variant. Indeed, in the second variant simulation,the bridging of Phe652, Phe648 and Phe639 is completely lost. In reality, the effect could be more severe on the structure during the protein folding.
c.2245C>T	R749W 2D AIThe SynGAP1 missense variant R749W is listed in ClinVar as benign and is observed in gnomAD (ID 6‑33441710‑C‑T). Prediction tools that classify the variant as benign include REVEL, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also returns benign, and Foldetta stability analysis is unavailable. Overall, the majority of evidence, especially from high‑confidence methods, supports a benign effect. This consensus aligns with the ClinVar designation, so there is no contradiction between the predictions and the reported clinical classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.675549	Disordered	0.626050	Binding	0.337	0.860	0.625	Likely Benign		1	6-33441710-C-T	3	1.86e-6	-7.647	In-Between	0.338	Likely Benign	Likely Benign	0.173	Likely Benign	0.1215	0.4088											-2.62	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.59	Benign	0.00	Affected	4.32	2	2	-3	3.6	30.03
c.2414T>A	L805Q 2D AIThe SynGAP1 missense variant L805Q is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default remains uncertain. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized predicts a benign effect, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans pathogenic (2 pathogenic vs. 1 benign, 1 uncertain). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the balance of evidence (five pathogenic vs. three benign predictions, with a pathogenic SGM Consensus) indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.775545	Disordered	0.827669	Binding	0.341	0.903	0.625							-6.244	Likely Benign	0.427	Ambiguous	Likely Benign	0.152	Likely Benign	0.1215	0.1265											-2.66	Deleterious	0.927	Possibly Damaging	0.690	Possibly Damaging	2.37	Pathogenic	0.00	Affected			-2	-2	-7.3	14.97
c.869T>G	L290R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change L290R is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools largely agree on a deleterious effect: benign predictions are limited to FoldX, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all classify the variant as pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenicity, the SGM‑Consensus also indicates likely pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) yields an uncertain result. Overall, the consensus of the majority of evidence points to a pathogenic impact. This conclusion is consistent with the absence of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.127496	Structured	0.399723	Uncertain	0.904	0.255	0.000							-13.938	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	0.705	Likely Pathogenic	0.1215	0.1056		0.48	Likely Benign	0.1	0.88	Ambiguous	0.68	Ambiguous	0.89	Ambiguous	-5.52	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.03	Pathogenic	0.01	Affected			-3	-2	-8.3	43.03
c.1303T>G	L435V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L435V has no ClinVar assertion and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and AlphaMissense‑Default. ESM1b is uncertain. High‑accuracy assessments further support a pathogenic bias: AlphaMissense‑Optimized predicts benign, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default (pathogenic), ESM1b (uncertain), FATHMM (benign), and PROVEAN (pathogenic)—favors pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenic. With the preponderance of pathogenic calls from both general and high‑accuracy tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.229226	Structured	0.333584	Uncertain	0.954	0.292	0.000							-7.134	In-Between	0.571	Likely Pathogenic	Likely Benign	0.217	Likely Benign	0.1216	0.2628		2.97	Destabilizing	0.1	2.33	Destabilizing	2.65	Destabilizing	1.36	Destabilizing	-2.80	Deleterious	0.995	Probably Damaging	0.970	Probably Damaging	3.23	Benign	0.06	Tolerated			2	1	0.4	-14.03
c.2158G>A	D720N 2D 3DClick to see structure in 3D Viewer AISynGAP1 D720N is listed in ClinVar as benign (ClinVar ID 2837618.0) and is present in gnomAD (ID 6‑33441623‑G‑A). Prediction tools that indicate a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus as pathogenic. With seven pathogenic versus six benign predictions overall, the variant is most likely pathogenic according to in‑silico evidence, which contradicts the benign classification in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.374039	Structured	0.450695	Uncertain	0.955	0.417	0.125	Likely Benign		1	6-33441623-G-A	5	3.10e-6	-9.135	Likely Pathogenic	0.654	Likely Pathogenic	Likely Benign	0.289	Likely Benign	0.1216	0.5513		0.01	Likely Benign	0.0	-0.20	Likely Benign	-0.10	Likely Benign	0.46	Likely Benign	-3.74	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	2.18	Pathogenic	0.01	Affected	3.50	9	1	2	0.0	-0.98
c.2533G>A	D845N 2D AIThe SynGAP1 missense variant D845N is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools show a split: benign predictions come from REVEL and ESM1b, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. When the high‑accuracy consensus is considered, AlphaMissense‑Optimized remains pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates pathogenicity. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a pathogenic effect, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.599971	Binding	0.297	0.827	0.500							-6.586	Likely Benign	0.961	Likely Pathogenic	Likely Pathogenic	0.264	Likely Benign	0.1216	0.7112											-3.42	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	1.96	Pathogenic	0.00	Affected			2	1	0.0	-0.98
c.3851T>G	L1284R 2D AIThe SynGAP1 missense variant L1284R is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs. 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward a pathogenic impact. This assessment does not contradict ClinVar status, as the variant has not yet been classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.812494	Disordered	0.824557	Binding	0.441	0.748	0.875							-4.203	Likely Benign	0.156	Likely Benign	Likely Benign	0.163	Likely Benign	0.1216	0.0488											-3.11	Deleterious	0.990	Probably Damaging	0.722	Possibly Damaging	2.48	Pathogenic	0.00	Affected			-3	-2	-8.3	43.03
c.1081C>G	Q361E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q361E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Uncertain predictions come from Rosetta, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts benign, while Foldetta remains uncertain. Taken together, the majority of evidence supports a benign impact for Q361E, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.305330	Structured	0.427593	Uncertain	0.945	0.534	0.250							-7.544	In-Between	0.289	Likely Benign	Likely Benign	0.153	Likely Benign	0.1217	0.3018		0.29	Likely Benign	0.0	1.02	Ambiguous	0.66	Ambiguous	0.21	Likely Benign	-0.89	Neutral	0.969	Probably Damaging	0.930	Probably Damaging	1.70	Pathogenic	0.26	Tolerated			2	2	0.0	0.98
c.1106C>G	T369R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T369R is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33438011‑C‑G). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are FATHMM and AlphaMissense‑Default. Rosetta and Foldetta are uncertain, so their results are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta is also uncertain. Overall, the majority of evidence (nine benign vs two pathogenic) supports a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.468512	Structured	0.437011	Uncertain	0.417	0.707	0.500				6-33438011-C-G	3	1.93e-6	-6.772	Likely Benign	0.571	Likely Pathogenic	Likely Benign	0.148	Likely Benign	0.1217	0.3737		-0.27	Likely Benign	0.1	1.48	Ambiguous	0.61	Ambiguous	0.29	Likely Benign	-2.15	Neutral	0.244	Benign	0.107	Benign	1.72	Pathogenic	0.32	Tolerated	3.42	19	-1	-1	-3.8	55.08
c.1296T>G	C432W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C432W is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments reinforce this: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus indicates a likely pathogenic status, and Foldetta (combining FoldX‑MD and Rosetta outputs) yields an uncertain result, providing no counter‑evidence. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a pathogenic effect. This conclusion is consistent with the absence of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.362533	Uncertain	0.960	0.285	0.000							-13.936	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	0.433	Likely Benign	0.1217	0.3246		1.17	Ambiguous	0.4	0.72	Ambiguous	0.95	Ambiguous	0.58	Ambiguous	-10.50	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	3.43	Benign	0.00	Affected			-8	-2	-3.4	83.07
c.1316T>G	L439R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change L439R lies in the GAP domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, while the remaining evaluated algorithms (SGM‑Consensus, REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic or likely pathogenic impact; FoldX is uncertain and is treated as unavailable. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.222385	Structured	0.281542	Uncertain	0.942	0.265	0.000							-12.870	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	0.554	Likely Pathogenic	0.1217	0.0488		1.90	Ambiguous	0.5	2.62	Destabilizing	2.26	Destabilizing	1.40	Destabilizing	-5.25	Deleterious	0.996	Probably Damaging	0.983	Probably Damaging	3.22	Benign	0.01	Affected			-3	-2	-8.3	43.03
c.1747G>C	D583H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D583H is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include Rosetta and premPS, whereas the majority of tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) predict a pathogenic outcome. FoldX and Foldetta provide uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Based on the overall consensus of the available predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.116183	Structured	0.038478	Uncertain	0.805	0.247	0.000							-9.191	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	0.713	Likely Pathogenic	0.1217	0.4182		1.22	Ambiguous	0.2	-0.07	Likely Benign	0.58	Ambiguous	-0.22	Likely Benign	-6.64	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.43	Pathogenic	0.03	Affected			1	-1	0.3	22.05
c.3095T>A	L1032Q 2D AIThe SynGAP1 missense variant L1032Q is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar) and SIFT. AlphaMissense‑Default remains uncertain. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the aggregate evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is assigned). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.865454	Disordered	0.995318	Binding	0.365	0.735	0.500							-2.992	Likely Benign	0.467	Ambiguous	Likely Benign	0.134	Likely Benign	0.1217	0.1677											-0.78	Neutral	0.995	Probably Damaging	0.892	Possibly Damaging	2.66	Benign	0.03	Affected			-2	-2	-7.3	14.97
c.3722T>A	L1241Q 2D AIThe SynGAP1 missense variant L1241Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: the single benign prediction comes from REVEL, while all other evaluated algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic effect. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, the variant is most likely pathogenic, and this conclusion is consistent with the absence of any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.545602	Disordered	0.488880	Uncertain	0.828	0.541	0.375							-10.429	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	0.386	Likely Benign	0.1217	0.0488											-4.65	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.61	Pathogenic	0.00	Affected			-2	-2	-7.3	14.97
c.1853A>G	Q618R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q618R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus, REVEL, FoldX, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome, while Rosetta and premPS are inconclusive. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts benign. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.175930	Structured	0.138725	Uncertain	0.904	0.240	0.000							-2.513	Likely Benign	0.207	Likely Benign	Likely Benign	0.285	Likely Benign	0.1218	0.1163		-0.43	Likely Benign	0.1	0.60	Ambiguous	0.09	Likely Benign	-0.66	Ambiguous	1.22	Neutral	0.005	Benign	0.009	Benign	-1.24	Pathogenic	1.00	Tolerated			1	1	-1.0	28.06
c.2630T>G	L877R 2D AIThe SynGAP1 missense variant L877R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict the ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.653063	Disordered	0.634010	Binding	0.265	0.875	0.250							-6.678	Likely Benign	0.673	Likely Pathogenic	Likely Benign	0.148	Likely Benign	0.1218	0.0761											-1.82	Neutral	0.986	Probably Damaging	0.876	Possibly Damaging	2.57	Benign	0.02	Affected			-3	-2	-8.3	43.03
c.1346G>C	S449T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S449T is not reported in ClinVar and is absent from gnomAD. All available in‑silico predictors classify it as benign: REVEL, FoldX, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool predicts pathogenicity. High‑accuracy assessments are consistent: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus predicts likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Based on these predictions, the variant is most likely benign, and this assessment does not contradict the ClinVar status (which has no entry). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.254060	Structured	0.301437	Uncertain	0.958	0.251	0.000							-6.262	Likely Benign	0.115	Likely Benign	Likely Benign	0.039	Likely Benign	0.1219	0.5077		0.36	Likely Benign	0.1	-0.46	Likely Benign	-0.05	Likely Benign	-0.15	Likely Benign	-1.48	Neutral	0.038	Benign	0.008	Benign	3.42	Benign	0.33	Tolerated			1	1	0.1	14.03
c.178G>A	D60N 2D AIThe SynGAP1 D60N missense variant has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.284882	Structured	0.480942	Uncertain	0.521	0.676	0.000							-3.610	Likely Benign	0.577	Likely Pathogenic	Likely Benign	0.128	Likely Benign	0.1219	0.8168											-0.22	Neutral	0.805	Possibly Damaging	0.857	Possibly Damaging	4.13	Benign	0.00	Affected			2	1	0.0	-0.98
c.2774T>A	L925H 2D AIThe SynGAP1 missense variant L925H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic.” No Foldetta stability result is available. Overall, the majority of evidence points to a pathogenic effect for L925H, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.977963	Binding	0.290	0.852	0.125							-3.369	Likely Benign	0.997	Likely Pathogenic	Likely Pathogenic	0.475	Likely Benign	0.1219	0.1494											-5.24	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.28	Pathogenic	0.00	Affected			-2	-3	-7.0	23.98
c.3293G>T	S1098I 2D AIThe SynGAP1 missense variant S1098I is catalogued in gnomAD (ID 6‑33443845‑G‑T) and has no ClinVar entry. All evaluated in‑silico predictors classify it as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool reports a pathogenic outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.973030	Binding	0.337	0.855	1.000				6-33443845-G-T			-4.497	Likely Benign	0.182	Likely Benign	Likely Benign	0.139	Likely Benign	0.1219	0.5601											-0.92	Neutral	0.259	Benign	0.066	Benign	2.67	Benign	0.15	Tolerated	3.77	5	-2	-1	5.3	26.08
c.2084T>G	L695R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L695R is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: benign predictions are limited to FATHMM, while the remaining 13 tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) all classify the variant as pathogenic. AlphaMissense‑Optimized returns an uncertain result. High‑accuracy assessments further support pathogenicity: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also pathogenic. Overall, the evidence overwhelmingly indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.118441	Structured	0.373419	Uncertain	0.942	0.258	0.000							-15.582	Likely Pathogenic	0.873	Likely Pathogenic	Ambiguous	0.605	Likely Pathogenic	0.1220	0.0530		2.05	Destabilizing	0.1	2.66	Destabilizing	2.36	Destabilizing	1.57	Destabilizing	-5.92	Deleterious	0.993	Probably Damaging	0.588	Possibly Damaging	3.17	Benign	0.00	Affected			-3	-2	-8.3	43.03
c.2998A>G	I1000V 2D AIThe SynGAP1 missense variant I1000V is listed in ClinVar (ID 2572013.0) with an “Uncertain” clinical significance and is not reported in gnomAD. Functional prediction tools that assess evolutionary conservation and structural impact (REVEL, SIFT, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default) all converge on a benign outcome. No tool in the dataset predicts pathogenicity. High‑accuracy predictors reinforce this consensus: AlphaMissense‑Optimized reports a benign effect, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict the ClinVar status, which remains uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.745909	Disordered	0.957020	Binding	0.293	0.904	0.625	Uncertain		2				-4.102	Likely Benign	0.098	Likely Benign	Likely Benign	0.086	Likely Benign	0.1220	0.3404											-0.20	Neutral	0.437	Benign	0.170	Benign	2.76	Benign	0.81	Tolerated	4.32	4	3	4	-0.3	-14.03
c.3091A>C	M1031L 2D AIThe SynGAP1 missense variant M1031L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Overall, the variant is most likely benign, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.865454	Disordered	0.995959	Binding	0.340	0.736	0.500							-2.213	Likely Benign	0.162	Likely Benign	Likely Benign	0.056	Likely Benign	0.1220	0.4050											-0.82	Neutral	0.044	Benign	0.018	Benign	2.84	Benign	0.33	Tolerated			4	2	1.9	-18.03
c.3091A>T	M1031L 2D AIThe SynGAP1 missense variant M1031L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Overall, the variant is most likely benign, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.865454	Disordered	0.995959	Binding	0.340	0.736	0.500							-2.213	Likely Benign	0.162	Likely Benign	Likely Benign	0.056	Likely Benign	0.1220	0.4050											-0.82	Neutral	0.044	Benign	0.018	Benign	2.84	Benign	0.33	Tolerated			4	2	1.9	-18.03
c.38T>A	I13N 2D AIThe SynGAP1 missense variant I13N is reported in gnomAD (ID 6‑33420302‑T‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts it to be pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it “Likely Benign.” High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign; Foldetta results are not available. Overall, the consensus of the majority of tools, including the high‑accuracy methods, indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.482657	Uncertain	0.318	0.916	0.375				6-33420302-T-A			-3.725	Likely Benign	0.237	Likely Benign	Likely Benign	0.096	Likely Benign	0.1220	0.1100											-0.16	Neutral	0.056	Benign	0.005	Benign	4.02	Benign	0.00	Affected	4.32	1	-3	-2	-8.0	0.94
c.817G>C	E273Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E273Q is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of individual predictors (seven benign vs. five pathogenic) lean toward a benign classification, while the SGM Consensus and AlphaMissense‑Optimized provide conflicting signals. Thus, the variant is most likely benign based on the aggregate predictions, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.071867	Structured	0.398918	Uncertain	0.863	0.196	0.125							-9.865	Likely Pathogenic	0.503	Ambiguous	Likely Benign	0.168	Likely Benign	0.1220	0.3130		-0.29	Likely Benign	0.1	-0.29	Likely Benign	-0.29	Likely Benign	-0.01	Likely Benign	-1.84	Neutral	0.946	Possibly Damaging	0.671	Possibly Damaging	1.77	Pathogenic	0.04	Affected			2	2	0.0	-0.98
c.1064G>T	G355V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G355V is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, Rosetta, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain or unavailable results are reported for FoldX, premPS, and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, whereas the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic effect. Foldetta’s stability prediction is unavailable. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.155435	Structured	0.388832	Uncertain	0.810	0.354	0.125							-10.111	Likely Pathogenic	0.675	Likely Pathogenic	Likely Benign	0.346	Likely Benign	0.1221	0.4685		1.78	Ambiguous	0.6	0.14	Likely Benign	0.96	Ambiguous	0.53	Ambiguous	-7.59	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.78	Pathogenic	0.04	Affected			-1	-3	4.6	42.08
c.2569A>T	S857C 2D AIThe SynGAP1 missense variant S857C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign. Foldetta results are unavailable, so they do not influence the overall assessment. Based on the majority of predictions and the high‑accuracy consensus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.475747	Uncertain	0.288	0.826	0.375							-6.335	Likely Benign	0.109	Likely Benign	Likely Benign	0.146	Likely Benign	0.1221	0.6672											-1.28	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	4.02	Benign	0.08	Tolerated			0	-1	3.3	16.06
c.2576G>A	S859N 2D AIThe SynGAP1 missense variant S859N is reported in ClinVar as “None” and is not present in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which contains no pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.497075	Uncertain	0.288	0.819	0.375							-8.184	Likely Pathogenic	0.225	Likely Benign	Likely Benign	0.142	Likely Benign	0.1221	0.5226											-0.62	Neutral	0.991	Probably Damaging	0.988	Probably Damaging	3.99	Benign	0.29	Tolerated			1	1	-2.7	27.03
c.268G>A	V90M 2D AIThe SynGAP1 missense variant V90M is listed in gnomAD (6‑33425876‑G‑A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status, as none is reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.570702	Disordered	0.542047	Binding	0.343	0.873	0.500				6-33425876-G-A	1	6.20e-7	-5.017	Likely Benign	0.463	Ambiguous	Likely Benign	0.053	Likely Benign	0.1221	0.4393											-0.15	Neutral	0.872	Possibly Damaging	0.162	Benign	3.98	Benign	0.00	Affected	4.32	1	1	2	-2.3	32.06
c.3788T>C	I1263T 2D AIThe SynGAP1 missense variant I1263T is listed in ClinVar with an “Uncertain” status and is present in the gnomAD database (ID 6‑33446780‑T‑C). Functional prediction tools largely agree on a deleterious effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report pathogenicity, while only ESM1b predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic classification. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of prediction tools and the high‑accuracy methods points to a pathogenic effect, which aligns with the ClinVar designation of uncertainty but does not contradict it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.425610	Structured	0.740957	Binding	0.867	0.574	0.000	Uncertain		1	6-33446780-T-C	2	1.24e-6	-6.564	Likely Benign	0.962	Likely Pathogenic	Likely Pathogenic	0.529	Likely Pathogenic	0.1221	0.1051											-4.15	Deleterious	0.946	Possibly Damaging	0.673	Possibly Damaging	1.81	Pathogenic	0.00	Affected	3.77	5	0	-1	-5.2	-12.05
c.775C>T	R259W 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R259W is listed in ClinVar with an uncertain significance (ClinVar ID 2014570.0) and is not reported in gnomAD. Functional prediction tools that agree on a benign effect are limited to FATHMM, whereas the remaining evaluated algorithms—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—consistently predict a pathogenic impact. Uncertain results are reported by FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, remains inconclusive. Overall, the preponderance of evidence indicates that R259W is most likely pathogenic, a conclusion that does not contradict the current ClinVar status of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.222385	Structured	0.338208	Uncertain	0.885	0.255	0.250	Uncertain		1				-12.186	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	0.691	Likely Pathogenic	0.1221	0.4269		1.95	Ambiguous	0.8	0.51	Ambiguous	1.23	Ambiguous	0.51	Ambiguous	-7.35	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	5.76	Benign	0.00	Affected	3.39	15	2	-3	3.6	30.03	254.0	40.0	0.2	0.2	0.2	0.4	X	X					X	Potentially Pathogenic	The guanidinium group of Arg259, located at the beginning of an anti-parallel β sheet strand (res. Arg259-Arg272), forms salt bridges with the carboxylate groups of Asp684 at the end of an α helix (res. Ile683-Gln702, GAP domain) and Asp261 on the same β strand. The Arg259 side chain also frequently forms hydrogen bonds with the backbone carbonyl groups of Ser257, Asn256, and Asp255. In the variant simulations, the indole ring of the Trp259 side chain cannot form salt bridges or maintain hydrogen bonding with the carboxylate group of Asp684 or other nearby residues. Notably, the amino group of the Lys254 side chain maintains a salt bridge with Asp684 and Glu244 throughout the variant simulations, while it forms a cation-π bond with the indole ring of Trp259 in the variant. This salt bridge is not maintained in the WT simulations. Additionally, the partially or loosely α helical conformation of a lysine-containing loop (res. Lys251-Ser257), which extends to a nearby α helix (res. Met414-Asn426), could be stabilized due to the residue swap. Moreover, the bulky size of the Trp259 side chain requires nearby residues to adjust their positioning to accommodate the introduced residue, weakening the tertiary structure assembly between the C2, PH, and GAP domains. The residue swap potentially causes more severe effects during protein folding or for the SynGAP-membrane interaction than the solvent-only simulations imply.
c.905C>G	S302C 2D AIThe SynGAP1 missense variant S302C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, FoldX, premPS, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Uncertain predictions come from Rosetta, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact for S302C, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.414856	Structured	0.263489	Uncertain	0.616	0.258	0.375							-7.290	In-Between	0.105	Likely Benign	Likely Benign	0.070	Likely Benign	0.1221	0.6514		0.32	Likely Benign	0.5	1.24	Ambiguous	0.78	Ambiguous	-0.04	Likely Benign	-0.83	Neutral	0.833	Possibly Damaging	0.455	Possibly Damaging	4.05	Benign	0.02	Affected			0	-1	3.3	16.06
c.2819G>T	G940V 2D AIThe SynGAP1 missense variant G940V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the consensus of available predictions points to a benign impact, and this is consistent with the lack of ClinVar evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.889439	Disordered	0.920635	Binding	0.383	0.902	0.625							-6.252	Likely Benign	0.078	Likely Benign	Likely Benign	0.110	Likely Benign	0.1222	0.3822											0.36	Neutral	0.626	Possibly Damaging	0.419	Benign	2.92	Benign	0.31	Tolerated			-1	-3	4.6	42.08
c.349A>T	S117C 2D AIThe SynGAP1 missense variant S117C is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.672422	Binding	0.357	0.877	0.625							-5.980	Likely Benign	0.201	Likely Benign	Likely Benign	0.246	Likely Benign	0.1222	0.5057											-1.81	Neutral	0.992	Probably Damaging	0.667	Possibly Damaging	3.68	Benign	0.00	Affected			0	-1	3.3	16.06
c.3743T>G	L1248R 2D AIThe SynGAP1 missense variant L1248R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. No Foldetta stability analysis is available for this variant. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.834292	Disordered	0.371716	Uncertain	0.880	0.562	0.625							-11.285	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.370	Likely Benign	0.1222	0.0488											-4.69	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.64	Pathogenic	0.00	Affected			-3	-2	-8.3	43.03
c.4028A>T	H1343L 2D AIThe SynGAP1 missense variant H1343L is reported in gnomAD (ID 6‑33451902‑A‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign status. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the consensus of the available predictions points to a benign effect, and this is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.910643	Disordered	0.983646	Binding	0.350	0.677	0.875				6-33451902-A-T			-1.552	Likely Benign	0.132	Likely Benign	Likely Benign	0.058	Likely Benign	0.1222	0.5869											-1.28	Neutral	0.053	Benign	0.012	Benign	4.07	Benign	0.00	Affected	4.32	1	-3	-2	7.0	-23.98
c.499G>A	D167N 2D AIThe SynGAP1 missense variant D167N is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33432796‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic, two benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the available predictions, the variant is most likely benign; this assessment does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.429200	Structured	0.502306	Binding	0.377	0.667	0.375				6-33432796-G-A	3	1.86e-6	-11.939	Likely Pathogenic	0.843	Likely Pathogenic	Ambiguous	0.097	Likely Benign	0.1222	0.7330											-2.32	Neutral	0.141	Benign	0.123	Benign	3.96	Benign	0.00	Affected	3.74	4	1	2	0.0	-0.98
c.1208A>T	K403I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K403I is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, premPS, and FATHMM, while the remaining tools—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict it to be pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of predictions (nine pathogenic vs. five benign) and the high‑accuracy tools lean toward a pathogenic effect. Thus, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.275179	Structured	0.424920	Uncertain	0.960	0.372	0.000							-15.239	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.519	Likely Pathogenic	0.1223	0.4141		0.17	Likely Benign	0.1	-0.46	Likely Benign	-0.15	Likely Benign	0.36	Likely Benign	-7.27	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.70	Benign	0.00	Affected			-2	-3	8.4	-15.01
c.1359C>A	H453Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H453Q is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic outcome: SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Tools with uncertain or inconclusive results—FoldX, Rosetta, premPS, AlphaMissense‑Optimized, and Foldetta—are treated as unavailable for pathogenicity assessment. High‑accuracy methods specifically show SGM‑Consensus as Likely Pathogenic, AlphaMissense‑Optimized as uncertain, and Foldetta as uncertain. Overall, the preponderance of evidence from consensus and high‑accuracy predictors indicates that H453Q is most likely pathogenic, and this assessment does not contradict the current ClinVar status, which contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.352862	Structured	0.316097	Uncertain	0.946	0.200	0.000							-10.894	Likely Pathogenic	0.893	Likely Pathogenic	Ambiguous	0.259	Likely Benign	0.1223	0.3112		0.90	Ambiguous	0.1	1.55	Ambiguous	1.23	Ambiguous	0.92	Ambiguous	-7.91	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	3.45	Benign	0.09	Tolerated			3	0	-0.3	-9.01
c.1359C>G	H453Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H453Q is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic outcome: SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Tools with uncertain or inconclusive results—FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized—are treated as unavailable for pathogenicity assessment. High‑accuracy methods specifically show SGM‑Consensus as Likely Pathogenic, AlphaMissense‑Optimized as Uncertain, and Foldetta as Uncertain. Overall, the preponderance of evidence points to a pathogenic effect for H453Q. This prediction does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.352862	Structured	0.316097	Uncertain	0.946	0.200	0.000							-10.894	Likely Pathogenic	0.893	Likely Pathogenic	Ambiguous	0.258	Likely Benign	0.1223	0.3112		0.90	Ambiguous	0.1	1.55	Ambiguous	1.23	Ambiguous	0.92	Ambiguous	-7.91	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	3.45	Benign	0.09	Tolerated			3	0	-0.3	-9.01
c.2108T>G	L703R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L703R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus) all classify the change as pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. The preponderance of pathogenic predictions, together with the high‑accuracy tools’ positive results, suggests that L703R is most likely pathogenic. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.144935	Structured	0.388282	Uncertain	0.929	0.353	0.000							-13.244	Likely Pathogenic	0.935	Likely Pathogenic	Ambiguous	0.459	Likely Benign	0.1223	0.0488		2.85	Destabilizing	0.0	3.74	Destabilizing	3.30	Destabilizing	1.79	Destabilizing	-4.92	Deleterious	0.994	Probably Damaging	0.806	Possibly Damaging	3.13	Benign	0.00	Affected			-3	-2	-8.3	43.03
c.2650C>T	R884W 2D AIThe SynGAP1 missense variant R884W is listed in ClinVar with an “Uncertain” status and is present in the gnomAD database (gnomAD ID 6‑33443202‑C‑T). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. No Foldetta (protein‑folding stability) result is available for this variant. Overall, the majority of computational predictions, including the high‑accuracy tools, indicate that R884W is most likely benign, which is consistent with the ClinVar “Uncertain” status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.720929	Disordered	0.641526	Binding	0.305	0.898	0.250	Uncertain		1	6-33443202-C-T	5	3.10e-6	-3.785	Likely Benign	0.332	Likely Benign	Likely Benign	0.151	Likely Benign	0.1223	0.3304											0.26	Neutral	0.995	Probably Damaging	0.812	Possibly Damaging	2.56	Benign	0.05	Affected	4.32	4	-3	2	3.6	30.03
c.3011A>T	H1004L 2D AIThe SynGAP1 missense variant H1004L is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (a majority vote among AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (two pathogenic vs two benign votes). Foldetta, which would provide a protein‑folding stability estimate, has no available result for this variant. Overall, the balance of evidence leans toward a benign interpretation, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.808535	Disordered	0.943707	Binding	0.271	0.901	0.750							-5.179	Likely Benign	0.716	Likely Pathogenic	Likely Benign	0.220	Likely Benign	0.1223	0.6026											-3.14	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.75	Benign	0.55	Tolerated			-2	-3	7.0	-23.98
c.718G>C	D240H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D240H missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include premPS and FATHMM, whereas the majority of tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; FoldX, Rosetta, and Foldetta are uncertain. High‑accuracy methods give a pathogenic verdict: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta remains uncertain. Overall, the consensus of the available predictions indicates that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.127496	Structured	0.343480	Uncertain	0.822	0.333	0.000							-14.551	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.865	Likely Pathogenic	0.1223	0.5398		1.14	Ambiguous	0.0	0.61	Ambiguous	0.88	Ambiguous	0.19	Likely Benign	-6.12	Deleterious	0.999	Probably Damaging	0.995	Probably Damaging	5.78	Benign	0.00	Affected			1	-1	0.3	22.05
c.220A>T	S74C 2D AIThe SynGAP1 missense variant S74C has no ClinVar entry and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.505461	Disordered	0.450156	Uncertain	0.294	0.831	0.500							-5.213	Likely Benign	0.089	Likely Benign	Likely Benign	0.048	Likely Benign	0.1224	0.4659											-1.29	Neutral	0.704	Possibly Damaging	0.089	Benign	4.04	Benign	0.00	Affected			0	-1	3.3	16.06
c.3092T>A	M1031K 2D AIThe SynGAP1 missense variant M1031K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.865454	Disordered	0.995959	Binding	0.340	0.736	0.500							-1.940	Likely Benign	0.709	Likely Pathogenic	Likely Benign	0.114	Likely Benign	0.1224	0.1412											-0.80	Neutral	0.325	Benign	0.098	Benign	2.66	Benign	0.18	Tolerated			0	-1	-5.8	-3.02
c.3705G>A	M1235I 2D AIThe SynGAP1 missense variant M1235I is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that classify the variant as benign include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only SIFT predicts a pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as “Likely Benign”; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.690604	Disordered	0.577958	Binding	0.872	0.532	0.125	Uncertain		1				-4.312	Likely Benign	0.310	Likely Benign	Likely Benign	0.027	Likely Benign	0.1224	0.2691											-1.44	Neutral	0.139	Benign	0.056	Benign	2.69	Benign	0.04	Affected	3.77	5	1	2	2.6	-18.03
c.3705G>C	M1235I 2D AIThe SynGAP1 missense variant M1235I is reported in gnomAD (6-33446697‑G‑C) and has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only SIFT predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar status (none). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.690604	Disordered	0.577958	Binding	0.872	0.532	0.125				6-33446697-G-C	1	6.20e-7	-4.312	Likely Benign	0.310	Likely Benign	Likely Benign	0.027	Likely Benign	0.1224	0.2691											-1.44	Neutral	0.139	Benign	0.056	Benign	2.69	Benign	0.04	Affected	3.77	5	1	2	2.6	-18.03
c.3705G>T	M1235I 2D AIThe SynGAP1 missense variant M1235I is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence supports a benign classification for M1235I, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.690604	Disordered	0.577958	Binding	0.872	0.532	0.125							-4.312	Likely Benign	0.310	Likely Benign	Likely Benign	0.027	Likely Benign	0.1224	0.2691											-1.44	Neutral	0.139	Benign	0.056	Benign	2.69	Benign	0.04	Affected	3.77	5	1	2	2.6	-18.03
c.73C>T	R25W 2D AIThe SynGAP1 missense variant R25W is listed in ClinVar with an “Uncertain” status (ClinVar ID 2993054.0) and is present in gnomAD (ID 6‑33423482‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign, while Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is not in conflict with the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.461924	Structured	0.438941	Uncertain	0.373	0.890	0.375	Uncertain		2	6-33423482-C-T	6	3.72e-6	-5.133	Likely Benign	0.549	Ambiguous	Likely Benign	0.158	Likely Benign	0.1224	0.3938											-1.60	Neutral	0.994	Probably Damaging	0.919	Probably Damaging	3.92	Benign	0.00	Affected	4.32	1	-3	2	3.6	30.03
c.1771G>A	A591T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A591T is listed in ClinVar with an uncertain significance designation and is observed in gnomAD (variant ID 6‑33440823‑G‑A). Functional prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic outcome. High‑accuracy assessments further show AlphaMissense‑Optimized as benign, SGM Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. No other folding‑stability metrics are available. Overall, the balance of evidence favors a pathogenic interpretation, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.018787	Structured	0.093848	Uncertain	0.882	0.185	0.000	Conflicting		3	6-33440823-G-A	18	1.12e-5	-9.572	Likely Pathogenic	0.704	Likely Pathogenic	Likely Benign	0.270	Likely Benign	0.1225	0.4155		1.61	Ambiguous	0.2	1.00	Ambiguous	1.31	Ambiguous	1.19	Destabilizing	-3.40	Deleterious	0.955	Possibly Damaging	0.209	Benign	3.48	Benign	0.01	Affected	3.37	35	1	0	-2.5	30.03	202.9	-43.4	0.2	0.0	0.7	0.1						X		Potentially Benign	The methyl group of the Ala591 side chain, located in the middle of an α helix (res. Glu582-Met603), packs against hydrophobic residues (e.g., Ile483, Phe484) of an opposing partially helical loop (res. Phe476-Asn487).In the variant simulations, the hydroxyl group of Thr591 can form hydrogen bonds with the backbone carbonyl of Ile843 in the opposing loop or the backbone carbonyl group of Arg587. These interactions could either reinforce the tertiary assembly or weaken the α helix unity. Additionally, the Thr591 side chain can hydrogen bond with the guanidinium group of the Arg587 side chain, potentially strengthening the α helix unity.Overall, the residue swap does not seem to cause any major negative effects on the protein structure.
c.1848T>A	D616E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D616E missense variant is catalogued in gnomAD (ID 6‑33440900‑T‑A) but has no ClinVar submission. Functional prediction tools show a split assessment: benign calls come from REVEL, both polyPhen‑2 HumDiv and HumVar, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls arise from PROVEAN, SIFT, and AlphaMissense‑Default. The remaining predictors (FoldX, Rosetta, Foldetta, premPS, ESM1b) are inconclusive. A high‑accuracy consensus (SGM) that aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN yields a pathogenic verdict. AlphaMissense‑Optimized remains benign, and Foldetta, which evaluates protein‑folding stability, is uncertain. Overall, the majority of evidence leans toward pathogenicity, and this conclusion does not conflict with ClinVar because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.129801	Structured	0.166689	Uncertain	0.867	0.252	0.000				6-33440900-T-A	1	6.20e-7	-7.250	In-Between	0.695	Likely Pathogenic	Likely Benign	0.092	Likely Benign	0.1225	0.4128		0.96	Ambiguous	0.1	1.52	Ambiguous	1.24	Ambiguous	0.58	Ambiguous	-2.85	Deleterious	0.421	Benign	0.232	Benign	3.32	Benign	0.03	Affected	3.37	35	2	3	0.0	14.03
c.1848T>G	D616E 2D 3DClick to see structure in 3D Viewer AISynGAP1 D616E is not reported in ClinVar but is present in gnomAD (ID 6‑33440900‑T‑G). Functional prediction tools that agree on benign impact include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, SIFT, and AlphaMissense‑Default. The remaining tools (FoldX, Rosetta, Foldetta, premPS, ESM1b) are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of conventional predictors lean toward a benign effect, but the high‑accuracy consensus is split, leaving the variant’s clinical significance unresolved. Thus, the variant is most likely benign based on the bulk of predictions, and this does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.129801	Structured	0.166689	Uncertain	0.867	0.252	0.000				6-33440900-T-G	3	1.86e-6	-7.250	In-Between	0.695	Likely Pathogenic	Likely Benign	0.092	Likely Benign	0.1225	0.4128		0.96	Ambiguous	0.1	1.52	Ambiguous	1.24	Ambiguous	0.58	Ambiguous	-2.85	Deleterious	0.421	Benign	0.232	Benign	3.32	Benign	0.03	Affected	3.37	35	2	3	0.0	14.03
c.2105A>G	Q702R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q702R is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Predictions that remain inconclusive are Rosetta, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to equal benign and pathogenic signals. Overall, the majority of available predictions lean toward a benign impact, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.074921	Structured	0.397258	Uncertain	0.907	0.345	0.000	Uncertain		1				-7.894	In-Between	0.348	Ambiguous	Likely Benign	0.294	Likely Benign	0.1225	0.0605		-0.31	Likely Benign	0.1	0.63	Ambiguous	0.16	Likely Benign	0.13	Likely Benign	-3.14	Deleterious	0.909	Possibly Damaging	0.889	Possibly Damaging	3.43	Benign	0.02	Affected	3.47	10	1	1	-1.0	28.06	270.3	-52.9	0.0	0.0	0.0	0.1		X						Potentially Pathogenic	The carboxamide side chain of Gln702 is located at the end and outer surface of an α-helix (res. Leu685-Gln702), where it does not directly form hydrogen bonds with any residues in the WT simulations. In the variant simulations, the positively charged guanidinium group of Arg702 forms a salt bridge with the negatively charged carboxylate group of Glu698 on the same helix and/or hydrogen bonds with the backbone carbonyl group of Ala438 on an opposite α-helix (res. Tyr428-Glu436). Consequently, the residue swap could strengthen the tertiary structure assembly, which could have either positive or negative effects on its function.
c.2138C>A	P713Q 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant P713Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, FoldX, Foldetta, and FATHMM, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). Uncertain calls are made by Rosetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments further highlight this discordance: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign effect. Overall, the majority of evidence leans toward a benign interpretation, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.393235	Uncertain	0.961	0.371	0.000							-10.253	Likely Pathogenic	0.875	Likely Pathogenic	Ambiguous	0.364	Likely Benign	0.1225	0.3388		0.26	Likely Benign	0.0	-0.77	Ambiguous	-0.26	Likely Benign	0.95	Ambiguous	-6.38	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.37	Benign	0.00	Affected			0	-1	-1.9	31.01
c.3236G>A	S1079N 2D AIThe SynGAP1 missense variant S1079N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority of the high‑accuracy tools) also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of predictions indicates that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.983887	Binding	0.307	0.900	0.750							-4.989	Likely Benign	0.505	Ambiguous	Likely Benign	0.026	Likely Benign	0.1225	0.4657											-0.97	Neutral	0.001	Benign	0.001	Benign	3.93	Benign	0.00	Affected			1	1	-2.7	27.03
c.335G>T	G112V 2D AIThe SynGAP1 missense variant G112V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.640153	Binding	0.332	0.867	0.750							-2.411	Likely Benign	0.230	Likely Benign	Likely Benign	0.159	Likely Benign	0.1225	0.4218											-3.39	Deleterious	0.421	Benign	0.108	Benign	3.96	Benign	0.00	Affected			-1	-3	4.6	42.08
c.2149C>G	L717V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L717V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Two tools predict a damaging effect: polyPhen‑2 HumDiv and polyPhen‑2 HumVar. Stability‑based methods (FoldX, Rosetta, Foldetta) return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as Likely Benign, and Foldetta as inconclusive. Taken together, the majority of evidence points to a benign impact. This conclusion is consistent with the absence of a ClinVar assertion, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.239899	Structured	0.429342	Uncertain	0.969	0.397	0.000							-6.164	Likely Benign	0.308	Likely Benign	Likely Benign	0.119	Likely Benign	0.1226	0.2489		1.53	Ambiguous	0.0	1.25	Ambiguous	1.39	Ambiguous	0.09	Likely Benign	-0.25	Neutral	0.995	Probably Damaging	0.970	Probably Damaging	3.38	Benign	0.51	Tolerated			2	1	0.4	-14.03
c.2450C>T	S817L 2D AIThe SynGAP1 missense variant S817L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and AlphaMissense‑Optimized, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.490133	Structured	0.727082	Binding	0.314	0.901	0.625							-7.612	In-Between	0.659	Likely Pathogenic	Likely Benign	0.226	Likely Benign	0.1226	0.5662											-3.90	Deleterious	0.997	Probably Damaging	0.945	Probably Damaging	2.41	Pathogenic	0.00	Affected			-3	-2	4.6	26.08
c.2753C>T	A918V 2D AIThe SynGAP1 missense variant A918V is listed in ClinVar with an “Uncertain” status and is present in gnomAD (gnomAD ID 6‑33443305‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; a Foldetta stability prediction is not available. Overall, the majority of evidence points to a benign impact, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.632174	Disordered	0.891459	Binding	0.317	0.860	0.250	Uncertain		3	6-33443305-C-T	2	1.24e-6	-3.684	Likely Benign	0.112	Likely Benign	Likely Benign	0.119	Likely Benign	0.1226	0.5586											-1.61	Neutral	0.980	Probably Damaging	0.782	Possibly Damaging	2.61	Benign	0.03	Affected	4.32	4	0	0	2.4	28.05
c.50C>G	S17C 2D AIThe SynGAP1 missense variant S17C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools (polyPhen‑2 HumDiv and SIFT) predict pathogenicity, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.483068	Structured	0.452228	Uncertain	0.341	0.910	0.375							-4.364	Likely Benign	0.279	Likely Benign	Likely Benign	0.044	Likely Benign	0.1226	0.6721											0.17	Neutral	0.486	Possibly Damaging	0.048	Benign	3.99	Benign	0.00	Affected			0	-1	3.3	16.06
c.25C>T	H9Y 2D AIThe SynGAP1 missense variant H9Y is reported in gnomAD (ID 6‑33420289‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts it to be pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus itself is likely benign. Foldetta results are not available, so they do not influence the assessment. Overall, the preponderance of evidence points to the variant being most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.528099	Binding	0.394	0.916	0.750				6-33420289-C-T			-3.833	Likely Benign	0.136	Likely Benign	Likely Benign	0.082	Likely Benign	0.1227	0.5024											-0.14	Neutral	0.047	Benign	0.006	Benign	4.24	Benign	0.00	Affected	4.32	1	2	0	1.9	26.03
c.2659C>A	P887T 2D AIThe SynGAP1 missense variant P887T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign,” while Foldetta results are unavailable. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.716283	Disordered	0.602269	Binding	0.348	0.925	0.500							-4.780	Likely Benign	0.068	Likely Benign	Likely Benign	0.076	Likely Benign	0.1228	0.3822											-1.47	Neutral	0.292	Benign	0.110	Benign	2.79	Benign	0.21	Tolerated			0	-1	0.9	3.99
c.2717T>G	L906R 2D AIThe SynGAP1 missense variant L906R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of standard predictors (5 vs 4) lean toward pathogenicity, while the high‑accuracy AlphaMissense‑Optimized predicts benign and the consensus remains unresolved. Thus, the variant is most likely pathogenic based on the current predictions, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.604312	Disordered	0.644316	Binding	0.315	0.920	0.250							-3.440	Likely Benign	0.769	Likely Pathogenic	Likely Benign	0.160	Likely Benign	0.1228	0.0947											-0.26	Neutral	1.000	Probably Damaging	0.990	Probably Damaging	2.18	Pathogenic	0.04	Affected			-3	-2	-8.3	43.03
c.1628T>G	L543R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L543R is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that assess pathogenicity all agree that the variant is deleterious: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic. No tool predicts a benign effect. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, indicates a pathogenic impact. All available predictions are concordant and supportive. Based on these computational assessments, the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.020918	Uncertain	0.963	0.314	0.000							-18.563	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.739	Likely Pathogenic	0.1229	0.0488		3.47	Destabilizing	1.2	8.02	Destabilizing	5.75	Destabilizing	1.64	Destabilizing	-5.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.89	Pathogenic	0.00	Affected			-3	-2	-8.3	43.03
c.2134G>C	G712R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G712R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors—PolyPhen‑2 HumDiv, PolyPhen‑2 HumVar, SIFT, ESM1b, PROVEAN, AlphaMissense‑Default, AlphaMissense‑Optimized, Foldetta, Rosetta, and the SGM Consensus—classify it as pathogenic. Two tools, FoldX and premPS, return uncertain results. High‑accuracy methods all support pathogenicity: AlphaMissense‑Optimized, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), and Foldetta each predict a deleterious effect. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.278302	Structured	0.384858	Uncertain	0.947	0.365	0.000							-11.776	Likely Pathogenic	0.963	Likely Pathogenic	Likely Pathogenic	0.458	Likely Benign	0.1229	0.4482		1.75	Ambiguous	0.0	4.68	Destabilizing	3.22	Destabilizing	0.82	Ambiguous	-6.58	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.35	Benign	0.01	Affected			-3	-2	-4.1	99.14
c.2638G>A	A880T 2D AIThe SynGAP1 missense variant A880T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic outcome, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of the majority of tools and the high‑accuracy predictions point to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.621441	Binding	0.309	0.874	0.250							-4.594	Likely Benign	0.083	Likely Benign	Likely Benign	0.097	Likely Benign	0.1229	0.6396											-0.75	Neutral	0.761	Possibly Damaging	0.399	Benign	2.61	Benign	0.29	Tolerated			1	0	-2.5	30.03
c.3109A>G	I1037V 2D AIThe SynGAP1 missense variant I1037V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of available predictions indicates that I1037V is most likely benign, and this conclusion is not contradicted by ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.939629	Disordered	0.986140	Binding	0.309	0.774	0.625							-2.326	Likely Benign	0.461	Ambiguous	Likely Benign	0.085	Likely Benign	0.1229	0.3985											-0.09	Neutral	0.421	Benign	0.128	Benign	2.76	Benign	0.93	Tolerated			4	3	-0.3	-14.03
c.2531T>G	L844R 2D AIThe SynGAP1 missense variant L844R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, while the majority of tools predict a pathogenic effect: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.595080	Disordered	0.611301	Binding	0.304	0.835	0.375							-9.355	Likely Pathogenic	0.904	Likely Pathogenic	Ambiguous	0.267	Likely Benign	0.1230	0.0947											-2.77	Deleterious	0.960	Probably Damaging	0.697	Possibly Damaging	2.60	Benign	0.01	Affected			-3	-2	-8.3	43.03
c.2813G>T	G938V 2D AIThe SynGAP1 missense variant G938V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence indicates that G938V is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.905695	Disordered	0.949795	Binding	0.318	0.883	0.625							-6.112	Likely Benign	0.153	Likely Benign	Likely Benign	0.123	Likely Benign	0.1230	0.3811											-0.81	Neutral	0.999	Probably Damaging	0.985	Probably Damaging	2.83	Benign	0.31	Tolerated			-1	-3	4.6	42.08
c.1423C>T	R475W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R475W is listed in ClinVar with an “Uncertain” status and is present in gnomAD (variant ID 6‑33438455‑C‑T). Prediction tools that agree on a benign effect include only Foldetta, whereas the remaining tools (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus) uniformly predict a pathogenic impact; FoldX, Rosetta, and premPS are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus as likely pathogenic, and Foldetta as benign. Overall, the majority of evidence points to a pathogenic effect, which does not contradict the ClinVar “Uncertain” classification but suggests that the variant is more likely pathogenic rather than benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.382696	Uncertain	0.852	0.261	0.000	Uncertain		1	6-33438455-C-T	1	6.20e-7	-13.235	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	0.725	Likely Pathogenic	0.1231	0.2785		1.44	Ambiguous	0.4	-0.92	Ambiguous	0.26	Likely Benign	0.56	Ambiguous	-7.56	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	-1.45	Pathogenic	0.00	Affected	3.39	28	2	-3	3.6	30.03	266.9	39.6	0.0	0.0	0.0	0.1	X	X		X				Potentially Pathogenic	In the WT simulations, the guanidinium group of Arg475, located near the end of an α-helix (res. Ala461-Phe476), stacks with the phenyl ring of Phe476 and forms a salt bridge with Glu472. Additionally, Arg475 occasionally forms another salt bridge with the carboxylate group of Glu486 on the α-α loop connecting the two α-helices (res. Ala461-Phe476 and Leu489-Glu519) at the GAP-Ras interface. Therefore, Arg475 potentially plays a key role in positioning the loop by interacting with Glu486, which is necessary for the positioning of the “arginine finger” (Arg485) and, ultimately, for RasGTPase activation.In the variant simulations, Trp475 moves and stacks with Arg479 on the proceeding α-α loop, disrupting the terminal end of the α-helix. Lastly, the potential effect of the residue swap on the SynGAP-Ras complex formation or GTPase activation cannot be fully addressed using the SynGAP solvent-only simulations.
c.20C>G	S7C 2D AIThe SynGAP1 missense variant S7C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, all of which are benign, and therefore SGM‑Consensus also predicts benign. AlphaMissense‑Optimized independently predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy tools indicates that the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.590140	Disordered	0.548467	Binding	0.386	0.922	0.750							-5.066	Likely Benign	0.125	Likely Benign	Likely Benign	0.111	Likely Benign	0.1231	0.5672											0.41	Neutral	0.000	Benign	0.000	Benign	4.05	Benign	0.00	Affected			0	-1	3.3	16.06
c.1285C>T	R429W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R429W is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33438190‑C‑T). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b; premPS and AlphaMissense‑Default are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of predictions lean toward a benign impact, and this does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.074921	Structured	0.390504	Uncertain	0.959	0.290	0.000	Conflicting		5	6-33438190-C-T	65	4.03e-5	-10.666	Likely Pathogenic	0.500	Ambiguous	Likely Benign	0.282	Likely Benign	0.1232	0.3422		0.31	Likely Benign	0.1	-0.13	Likely Benign	0.09	Likely Benign	0.52	Ambiguous	-3.19	Deleterious	1.000	Probably Damaging	0.990	Probably Damaging	3.41	Benign	0.03	Affected	3.38	25	2	-3	3.6	30.03	252.3	45.5	0.0	0.0	0.2	0.1		X						Potentially Pathogenic	The guanidinium group of Arg429, located in an α helix (res. Met414-Glu436), either forms a salt bridge with the carboxylate group of an acidic residue (Asp474, Asp467) or a H-bond with the hydroxyl group of Ser471 in an opposing α helix (res. Ala461-Phe476). In the variant simulations, the indole ring of the Trp429 side chain cannot form ionic interactions with the acidic residues. Although it forms a H-bond with Ser471, the bonding is not as strong as that of arginine. The residue swap could affect the tertiary structure assembly during folding; however, no large-scale negative effects were seen during the simulations.
c.1322T>A	V441D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V441D is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, and Foldetta, whereas a majority of tools (SGM Consensus, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. FoldX and Rosetta are inconclusive, and AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show that the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenicity, while Foldetta predicts benign stability. Overall, the balance of evidence leans toward pathogenicity, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.161087	Structured	0.259875	Uncertain	0.918	0.249	0.000							-15.392	Likely Pathogenic	0.934	Likely Pathogenic	Ambiguous	0.308	Likely Benign	0.1232	0.0698		-0.57	Ambiguous	0.1	0.56	Ambiguous	-0.01	Likely Benign	1.15	Destabilizing	-6.07	Deleterious	1.000	Probably Damaging	0.959	Probably Damaging	3.38	Benign	0.10	Tolerated			-2	-3	-7.7	15.96
c.2990C>T	A997V 2D AIThe SynGAP1 missense variant A997V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect. The prediction is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.948624	Binding	0.273	0.901	0.500							-4.504	Likely Benign	0.082	Likely Benign	Likely Benign	0.052	Likely Benign	0.1232	0.6335											-1.01	Neutral	0.369	Benign	0.120	Benign	4.15	Benign	0.00	Affected			0	0	2.4	28.05
c.3044C>T	T1015I 2D AIThe SynGAP1 missense variant T1015I is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for T1015I, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.788093	Disordered	0.928486	Binding	0.295	0.823	0.625							-4.713	Likely Benign	0.326	Likely Benign	Likely Benign	0.058	Likely Benign	0.1232	0.4871											-2.06	Neutral	0.586	Possibly Damaging	0.172	Benign	2.53	Benign	0.07	Tolerated			0	-1	5.2	12.05
c.1422C>A	D474E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D474E missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, and SIFT, whereas a separate group predicts pathogenicity: SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. Two tools are uncertain: ESM1b and AlphaMissense‑Optimized. High‑accuracy assessments show SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, AlphaMissense‑Optimized as Uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of predictions lean toward pathogenicity, but the high‑accuracy tools provide conflicting evidence. Thus, the variant is most likely pathogenic based on the current computational predictions, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.373433	Uncertain	0.864	0.255	0.000							-7.079	In-Between	0.874	Likely Pathogenic	Ambiguous	0.408	Likely Benign	0.1233	0.4287		-0.35	Likely Benign	0.1	0.05	Likely Benign	-0.15	Likely Benign	0.10	Likely Benign	-3.01	Deleterious	0.929	Possibly Damaging	0.938	Probably Damaging	-1.11	Pathogenic	0.20	Tolerated			3	2	0.0	14.03
c.1422C>G	D474E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D474E is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, and SIFT, while those that agree on a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. Two tools—AlphaMissense‑Optimized and ESM1b—return uncertain results. High‑accuracy assessments show SGM‑Consensus predicting a likely pathogenic outcome, AlphaMissense‑Optimized remaining uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicting a benign effect. Overall, the majority of consensus tools lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.102787	Structured	0.373433	Uncertain	0.864	0.255	0.000							-7.079	In-Between	0.874	Likely Pathogenic	Ambiguous	0.408	Likely Benign	0.1233	0.4287		-0.35	Likely Benign	0.1	0.05	Likely Benign	-0.15	Likely Benign	0.10	Likely Benign	-3.01	Deleterious	0.929	Possibly Damaging	0.938	Probably Damaging	-1.11	Pathogenic	0.20	Tolerated			3	2	0.0	14.03
c.2672T>G	L891R 2D AIThe SynGAP1 missense variant L891R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar) and SIFT. AlphaMissense‑Default remains uncertain. The high‑accuracy consensus methods reinforce the benign assessment: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign,” and the protein‑folding stability tool Foldetta has no available result for this variant. Based on the aggregate evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.712013	Disordered	0.505861	Binding	0.305	0.923	0.750							-4.120	Likely Benign	0.419	Ambiguous	Likely Benign	0.122	Likely Benign	0.1233	0.0863											-1.83	Neutral	0.970	Probably Damaging	0.801	Possibly Damaging	2.65	Benign	0.01	Affected			-3	-2	-8.3	43.03
c.766A>C	N256H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N256H is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include Rosetta, Foldetta, premPS, and FATHMM. Those that predict pathogenicity are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). The high‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic, whereas Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.414856	Structured	0.234105	Uncertain	0.826	0.271	0.250							-8.090	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.698	Likely Pathogenic	0.1233	0.5646		0.56	Ambiguous	0.3	0.26	Likely Benign	0.41	Likely Benign	0.08	Likely Benign	-4.06	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	5.82	Benign	0.05	Affected			2	1	0.3	23.04
c.1593C>G	C531W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C531W is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a deleterious effect include REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, all of which classify the change as pathogenic. Tools with uncertain or mixed outputs are Rosetta (uncertain) and premPS (uncertain). High‑accuracy assessments further support a damaging impact: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability predictions, also reports pathogenic. Based on the overwhelming agreement among pathogenic predictions and the corroborating high‑accuracy tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.281712	Structured	0.017941	Uncertain	0.878	0.401	0.000							-14.107	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	0.510	Likely Pathogenic	0.1234	0.3074		5.27	Destabilizing	3.4	0.63	Ambiguous	2.95	Destabilizing	0.70	Ambiguous	-9.12	Deleterious	0.998	Probably Damaging	0.871	Possibly Damaging	-1.25	Pathogenic	0.00	Affected			-8	-2	-3.4	83.07
c.1615C>A	H539N 2D 3DClick to see structure in 3D Viewer AISynGAP1 H539N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from FoldX, Foldetta, SIFT, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further clarify the variant’s impact: AlphaMissense‑Optimized predicts a benign effect, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic outcome, and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, reports a benign change. No prediction or stability result is missing or inconclusive. Overall, the majority of evidence points toward a pathogenic effect, which does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.031398	Uncertain	0.948	0.360	0.000							-8.685	Likely Pathogenic	0.751	Likely Pathogenic	Likely Benign	0.647	Likely Pathogenic	0.1234	0.1281		0.12	Likely Benign	0.1	0.78	Ambiguous	0.45	Likely Benign	0.72	Ambiguous	-5.93	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-0.89	Pathogenic	0.26	Tolerated			2	1	-0.3	-23.04
c.2588T>G	L863R 2D AIThe SynGAP1 missense variant L863R is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the majority of high‑accuracy predictors (AlphaMissense‑Optimized and the SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also support a benign classification. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact, but these are the only tools in disagreement. The AlphaMissense‑Default score is uncertain, and no Foldetta stability assessment is available. Overall, the preponderance of evidence points to a benign effect for the variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.594839	Binding	0.267	0.795	0.250							-6.402	Likely Benign	0.488	Ambiguous	Likely Benign	0.129	Likely Benign	0.1234	0.0947											-1.36	Neutral	0.999	Probably Damaging	0.977	Probably Damaging	4.02	Benign	0.09	Tolerated			-3	-2	-8.3	43.03
c.2243T>A	L748Q 2D AIThe SynGAP1 missense variant L748Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for L748Q, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.611637	Binding	0.339	0.863	0.750							-3.177	Likely Benign	0.119	Likely Benign	Likely Benign	0.060	Likely Benign	0.1235	0.1246											-0.46	Neutral	0.912	Possibly Damaging	0.611	Possibly Damaging	2.74	Benign	0.01	Affected			-2	-2	-7.3	14.97
c.2277G>A	M759I 2D AIThe SynGAP1 missense variant M759I is listed in ClinVar (ID 3686687.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33441742‑G‑A). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.879389	Binding	0.299	0.864	0.375	Uncertain		1	6-33441742-G-A	1	6.20e-7	-4.058	Likely Benign	0.393	Ambiguous	Likely Benign	0.075	Likely Benign	0.1235	0.3129											-0.88	Neutral	0.454	Possibly Damaging	0.192	Benign	2.83	Benign	0.34	Tolerated	3.99	5	1	2	2.6	-18.03
c.2277G>C	M759I 2D AIThe SynGAP1 missense variant M759I is catalogued in gnomAD (6‑33441742‑G‑C) and has no ClinVar entry. Consensus from multiple in‑silico predictors points to a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all score the variant as benign, while only polyPhen‑2 HumDiv flags it as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as “Likely Benign.” High‑accuracy tools reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta results are not available, so they do not influence the assessment. Overall, the computational evidence overwhelmingly supports a benign classification, and this is consistent with the absence of a pathogenic ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.879389	Binding	0.299	0.864	0.375				6-33441742-G-C			-4.058	Likely Benign	0.393	Ambiguous	Likely Benign	0.075	Likely Benign	0.1235	0.3129											-0.88	Neutral	0.454	Possibly Damaging	0.192	Benign	2.83	Benign	0.34	Tolerated	3.99	5	1	2	2.6	-18.03
c.2277G>T	M759I 2D AIThe SynGAP1 missense variant M759I is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status is unavailable. Overall, the preponderance of evidence from multiple prediction algorithms and high‑accuracy tools points to a benign impact for M759I, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.879389	Binding	0.299	0.864	0.375							-4.058	Likely Benign	0.393	Ambiguous	Likely Benign	0.075	Likely Benign	0.1235	0.3129											-0.88	Neutral	0.454	Possibly Damaging	0.192	Benign	2.83	Benign	0.34	Tolerated	3.99	5	1	2	2.6	-18.03
c.2326G>T	G776C 2D AIThe SynGAP1 missense variant G776C is not reported in ClinVar but is present in gnomAD (ID 6‑33442484‑G‑T). Prediction tools cluster into benign (REVEL, FATHMM, AlphaMissense‑Optimized) and pathogenic (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT). Two tools (ESM1b, AlphaMissense‑Default) return uncertain results. High‑accuracy assessments are limited: AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta data are unavailable. Overall, the majority of conventional predictors indicate pathogenicity, whereas the single high‑accuracy tool suggests benign. Given the preponderance of pathogenic predictions and the absence of a ClinVar entry, the variant is most likely pathogenic and does not contradict any existing ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.377384	Structured	0.886983	Binding	0.296	0.888	0.250				6-33442484-G-T			-7.974	In-Between	0.380	Ambiguous	Likely Benign	0.181	Likely Benign	0.1235	0.4403											-2.59	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	4.15	Benign	0.01	Affected	3.64	6	-3	-3	2.9	46.09
c.2702C>T	A901V 2D AIThe SynGAP1 missense variant A901V is listed in ClinVar (ID 934469.0) with an “Uncertain” clinical significance and is present in the gnomAD database (gnomAD ID 6‑33443254‑C‑T). All evaluated in‑silico predictors classify the substitution as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool reports a pathogenic or likely pathogenic outcome. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant. Overall, the computational evidence strongly supports a benign effect, which does not contradict the ClinVar “Uncertain” status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.595080	Disordered	0.489838	Uncertain	0.306	0.917	0.375	Uncertain		2	6-33443254-C-T	2	1.24e-6	-5.043	Likely Benign	0.219	Likely Benign	Likely Benign	0.029	Likely Benign	0.1235	0.6445											-1.83	Neutral	0.106	Benign	0.009	Benign	2.64	Benign	0.17	Tolerated	3.77	5	0	0	2.4	28.05
c.3892C>G	Q1298E 2D AIThe SynGAP1 missense variant Q1298E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions is benign, and this conclusion does not contradict any ClinVar annotation (none present). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.823549	Disordered	0.895297	Binding	0.410	0.821	0.750							-3.530	Likely Benign	0.156	Likely Benign	Likely Benign	0.098	Likely Benign	0.1235	0.1330											-1.14	Neutral	0.026	Benign	0.018	Benign	2.83	Benign	0.06	Tolerated			2	2	0.0	0.98
c.974T>A	L325Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L325Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly classify it as pathogenic. Benign predictions are absent; all evaluated algorithms—REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—return pathogenic or likely pathogenic calls. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports pathogenic. Consequently, the variant is most likely pathogenic, with no conflict with ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.352862	Structured	0.424577	Uncertain	0.955	0.436	0.000							-17.005	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.547	Likely Pathogenic	0.1235	0.1405		3.23	Destabilizing	0.0	2.68	Destabilizing	2.96	Destabilizing	2.02	Destabilizing	-3.97	Deleterious	0.999	Probably Damaging	0.977	Probably Damaging	1.33	Pathogenic	0.00	Affected			-2	-2	-7.3	14.97
c.2290A>C	N764H 2D AIThe SynGAP1 missense variant N764H is reported in gnomAD (ID 6‑33441755‑A‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Pathogenic predictions are made by polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability result is available. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar classification (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.380708	Structured	0.919527	Binding	0.305	0.861	0.250				6-33441755-A-C			-4.954	Likely Benign	0.320	Likely Benign	Likely Benign	0.091	Likely Benign	0.1236	0.5056											-2.09	Neutral	0.998	Probably Damaging	0.985	Probably Damaging	2.59	Benign	0.02	Affected	3.64	6	1	2	0.3	23.04
c.2660C>A	P887H 2D AIThe SynGAP1 missense variant P887H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for P887H, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.716283	Disordered	0.602269	Binding	0.348	0.925	0.500							-4.900	Likely Benign	0.136	Likely Benign	Likely Benign	0.072	Likely Benign	0.1236	0.3275											-1.71	Neutral	0.977	Probably Damaging	0.777	Possibly Damaging	2.73	Benign	0.13	Tolerated			0	-2	-1.6	40.02
c.1036G>C	V346L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V346L is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, and SIFT, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Four tools (Foldetta, premPS, AlphaMissense‑Optimized, and Rosetta) give uncertain or inconclusive results and are not used as evidence. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of reliable predictors and the SGM‑Consensus support a pathogenic effect. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.260850	Structured	0.350921	Uncertain	0.949	0.461	0.000							-8.178	Likely Pathogenic	0.834	Likely Pathogenic	Ambiguous	0.384	Likely Benign	0.1237	0.5348		0.05	Likely Benign	0.2	1.10	Ambiguous	0.58	Ambiguous	0.60	Ambiguous	-2.68	Deleterious	0.994	Probably Damaging	0.970	Probably Damaging	1.58	Pathogenic	0.09	Tolerated			2	1	-0.4	14.03
c.1036G>T	V346L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V346L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, and SIFT, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Four tools (Foldetta, premPS, AlphaMissense‑Optimized, and Rosetta) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points toward a deleterious effect. Therefore, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.260850	Structured	0.350921	Uncertain	0.949	0.461	0.000							-8.178	Likely Pathogenic	0.834	Likely Pathogenic	Ambiguous	0.386	Likely Benign	0.1237	0.5348		0.05	Likely Benign	0.2	1.10	Ambiguous	0.58	Ambiguous	0.60	Ambiguous	-2.68	Deleterious	0.994	Probably Damaging	0.970	Probably Damaging	1.58	Pathogenic	0.09	Tolerated			2	1	-0.4	14.03
c.1306G>C	E436Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E436Q is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include premPS and FATHMM, while the majority of tools predict a pathogenic outcome: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Tools with uncertain or inconclusive results are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the consensus of pathogenic predictions outweighs benign ones, and the high‑accuracy tools reinforce a pathogenic classification. Therefore, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.239899	Structured	0.321046	Uncertain	0.934	0.289	0.000							-12.413	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	0.607	Likely Pathogenic	0.1237	0.5809		0.51	Ambiguous	0.1	1.58	Ambiguous	1.05	Ambiguous	0.50	Likely Benign	-2.76	Deleterious	0.992	Probably Damaging	0.946	Probably Damaging	4.64	Benign	0.01	Affected			2	2	0.0	-0.98
c.2648T>G	L883R 2D AIThe SynGAP1 missense variant L883R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are not available. Overall, the preponderance of evidence points to a benign impact for the L883R variant, and this conclusion is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.716283	Disordered	0.641952	Binding	0.334	0.886	0.250							-3.026	Likely Benign	0.286	Likely Benign	Likely Benign	0.110	Likely Benign	0.1237	0.1147											-0.83	Neutral	0.934	Possibly Damaging	0.435	Benign	2.73	Benign	0.11	Tolerated			-3	-2	-8.3	43.03
c.1600T>A	S534T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S534T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all indicate benign or likely benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores benign, the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Thus, the overall evidence strongly supports a benign classification, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.167087	Structured	0.032173	Uncertain	0.860	0.362	0.000							-4.925	Likely Benign	0.104	Likely Benign	Likely Benign	0.200	Likely Benign	0.1238	0.5064		0.10	Likely Benign	0.1	0.46	Likely Benign	0.28	Likely Benign	0.19	Likely Benign	-2.42	Neutral	0.676	Possibly Damaging	0.933	Probably Damaging	3.32	Benign	0.07	Tolerated			1	1	0.1	14.03
c.2081C>T	A694V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A694V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, premPS, SIFT, AlphaMissense‑Default, AlphaMissense‑Optimized, and polyPhen2_HumVar. Tools that predict a pathogenic effect are PROVEAN and polyPhen2_HumDiv, while Rosetta and ESM1b give uncertain results. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is benign; and Foldetta is benign. No prediction or stability result is missing or inconclusive. Overall, the majority of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.127496	Structured	0.352199	Uncertain	0.938	0.269	0.000							-7.099	In-Between	0.221	Likely Benign	Likely Benign	0.149	Likely Benign	0.1238	0.4771		0.46	Likely Benign	0.1	-0.76	Ambiguous	-0.15	Likely Benign	0.24	Likely Benign	-2.66	Deleterious	0.970	Probably Damaging	0.207	Benign	3.42	Benign	0.08	Tolerated			0	0	2.4	28.05
c.3253C>T	R1085W 2D AISynGAP1 missense variant R1085W is listed in ClinVar as Uncertain and is present in gnomAD (ID 6‑33443805‑C‑T). Prediction tools that classify the variant as benign include REVEL, ESM1b, and FATHMM, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is Uncertain, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta stability assessment are unavailable. Overall, the majority of available predictions (five pathogenic vs. three benign) indicate a pathogenic effect. Thus, the variant is most likely pathogenic, which contradicts the ClinVar designation of Uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.852992	Disordered	0.978838	Binding	0.270	0.888	1.000	Uncertain		1	6-33443805-C-T	2	1.26e-6	-6.339	Likely Benign	0.821	Likely Pathogenic	Ambiguous	0.202	Likely Benign	0.1238	0.3700											-3.15	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.70	Benign	0.00	Affected	3.77	5	-3	2	3.6	30.03
c.538T>A	S180T 2D AIThe SynGAP1 missense variant S180T is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. three pathogenic) support a benign classification. This consensus does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Thus, the variant is most likely benign based on current predictive evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.509769	Disordered	0.442877	Uncertain	0.320	0.616	0.500							-9.851	Likely Pathogenic	0.669	Likely Pathogenic	Likely Benign	0.114	Likely Benign	0.1238	0.5171											-2.07	Neutral	0.057	Benign	0.020	Benign	3.86	Benign	0.02	Affected			1	1	0.1	14.03
c.1633A>C	M545L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M545L is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include SIFT, FoldX, Rosetta, and Foldetta. Those that predict a pathogenic effect comprise SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. Predictions that are uncertain or inconclusive are AlphaMissense‑Optimized, premPS, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of available predictions lean toward pathogenicity, and this conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.012875	Uncertain	0.955	0.311	0.000							-7.163	In-Between	0.914	Likely Pathogenic	Ambiguous	0.638	Likely Pathogenic	0.1239	0.2802		0.06	Likely Benign	0.1	0.26	Likely Benign	0.16	Likely Benign	0.79	Ambiguous	-2.72	Deleterious	0.732	Possibly Damaging	0.795	Possibly Damaging	-1.26	Pathogenic	0.40	Tolerated			4	2	1.9	-18.03
c.1633A>T	M545L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M545L has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from FoldX, Rosetta, Foldetta, and SIFT, while pathogenic predictions are made by SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. Uncertain results are reported by premPS, ESM1b, and AlphaMissense‑Optimized. High‑accuracy assessments show that AlphaMissense‑Optimized is inconclusive, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. Overall, seven tools predict pathogenicity versus four predicting benign, with three uncertain. Therefore, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.012875	Uncertain	0.955	0.311	0.000							-7.163	In-Between	0.914	Likely Pathogenic	Ambiguous	0.639	Likely Pathogenic	0.1239	0.2802		0.06	Likely Benign	0.1	0.26	Likely Benign	0.16	Likely Benign	0.79	Ambiguous	-2.72	Deleterious	0.732	Possibly Damaging	0.795	Possibly Damaging	-1.26	Pathogenic	0.40	Tolerated			4	2	1.9	-18.03
c.2504T>G	L835R 2D AIThe SynGAP1 missense variant L835R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic outcome. AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized independently predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this assessment does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.608892	Disordered	0.642742	Binding	0.319	0.863	0.125							-4.749	Likely Benign	0.381	Ambiguous	Likely Benign	0.126	Likely Benign	0.1239	0.0804											-1.05	Neutral	0.996	Probably Damaging	0.955	Probably Damaging	2.70	Benign	0.02	Affected			-3	-2	-8.3	43.03
c.3080A>C	N1027T 2D AIThe SynGAP1 missense variant N1027T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only polyPhen‑2 HumDiv indicates a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign and the SGM‑Consensus also reports Likely Benign; Foldetta results are not available. Overall, the consensus of the available predictions points to a benign effect, and this conclusion is consistent with the absence of any ClinVar assertion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.831250	Disordered	0.994357	Binding	0.347	0.745	0.500							-3.604	Likely Benign	0.199	Likely Benign	Likely Benign	0.046	Likely Benign	0.1239	0.7188											-0.71	Neutral	0.481	Possibly Damaging	0.220	Benign	2.75	Benign	0.13	Tolerated			0	0	2.8	-13.00
c.3119G>T	G1040V 2D AIThe SynGAP1 missense variant G1040V is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443671‑G‑T). Prediction tools that agree on a benign effect are ESM1b and AlphaMissense‑Optimized; those that predict a pathogenic effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta results are unavailable. Overall, the majority of predictions indicate a pathogenic impact, and this is not in conflict with the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.964893	Disordered	0.973805	Binding	0.332	0.816	0.625	Uncertain		1	6-33443671-G-T	4	2.48e-6	-3.453	Likely Benign	0.645	Likely Pathogenic	Likely Benign	0.774	Likely Pathogenic	0.1239	0.4213											-2.89	Deleterious	0.827	Possibly Damaging	0.456	Possibly Damaging	-0.74	Pathogenic	0.01	Affected	3.77	5	-1	-3	4.6	42.08
c.3577G>C	D1193H 2D AIThe SynGAP1 missense variant D1193H is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into three groups: benign predictions from REVEL, PROVEAN, and FATHMM; pathogenic predictions from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default; and uncertain predictions from ESM1b and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized inconclusive, an SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) that is benign, and no Foldetta result available. Overall, the majority of conventional tools predict pathogenicity, while the SGM Consensus suggests benign. Based on the combined evidence, the variant is most likely pathogenic, and this assessment does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.585406	Disordered	0.433390	Uncertain	0.807	0.600	0.375							-7.633	In-Between	0.900	Likely Pathogenic	Ambiguous	0.400	Likely Benign	0.1239	0.4584											-2.31	Neutral	0.977	Probably Damaging	0.924	Probably Damaging	5.41	Benign	0.00	Affected			1	-1	0.3	22.05
c.3076G>A	D1026N 2D AIThe SynGAP1 D1026N variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN and therefore reports a likely benign outcome. AlphaMissense‑Optimized also predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.894241	Disordered	0.993931	Binding	0.324	0.739	0.500							-4.166	Likely Benign	0.608	Likely Pathogenic	Likely Benign	0.117	Likely Benign	0.1240	0.5060											-2.07	Neutral	0.411	Benign	0.239	Benign	2.55	Benign	0.01	Affected			2	1	0.0	-0.98
c.3524G>T	R1175L 2D AISynGAP1 missense variant R1175L is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign predictions come from PROVEAN, ESM1b, and FATHMM, while pathogenic predictions arise from REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized is Uncertain, SGM‑Consensus remains Likely Benign, and Foldetta data are unavailable. Overall, the majority of individual predictors lean toward pathogenicity, yet the consensus of the most reliable tools suggests a benign outcome, leaving the variant’s clinical significance ambiguous. Consequently, the variant is most likely pathogenic based on the bulk of predictions, and this assessment does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.538167	Disordered	0.589347	Binding	0.545	0.732	0.375							-2.560	Likely Benign	0.876	Likely Pathogenic	Ambiguous	0.535	Likely Pathogenic	0.1240	0.2849											-2.37	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	5.38	Benign	0.00	Affected			-3	-2	8.3	-43.03
c.1367A>G	Q456R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q456R has no ClinVar entry and is not reported in gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, and FATHMM. Those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain; the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, whereas Foldetta (a folding‑stability method combining FoldX‑MD and Rosetta outputs) predicts benign. No evidence from the data contradicts ClinVar status, which is currently unclassified. Based on the available predictions, the variant is most likely benign, though the evidence is conflicting and does not conflict with the lack of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.170161	Structured	0.302348	Uncertain	0.939	0.164	0.000							-11.326	Likely Pathogenic	0.801	Likely Pathogenic	Ambiguous	0.295	Likely Benign	0.1241	0.1124		0.21	Likely Benign	0.1	0.12	Likely Benign	0.17	Likely Benign	0.33	Likely Benign	-3.69	Deleterious	0.980	Probably Damaging	0.943	Probably Damaging	3.37	Benign	0.20	Tolerated			1	1	-1.0	28.06
c.2792T>G	L931R 2D AIThe SynGAP1 missense variant L931R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only REVEL, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus remains pathogenic; Foldetta results are not available. Overall, the preponderance of evidence from multiple in‑silico predictors indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.549308	Disordered	0.989212	Binding	0.335	0.856	0.375							-8.606	Likely Pathogenic	0.933	Likely Pathogenic	Ambiguous	0.344	Likely Benign	0.1241	0.1205											-3.48	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.39	Pathogenic	0.01	Affected			-3	-2	-8.3	43.03
c.543C>A	H181Q 2D AIThe SynGAP1 missense variant H181Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic, two benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy tools therefore give a benign prediction from AlphaMissense‑Optimized, an inconclusive SGM Consensus, and no Foldetta data. Overall, the majority of predictions (six benign vs. three pathogenic) indicate that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.505461	Disordered	0.439530	Uncertain	0.294	0.616	0.500							-9.577	Likely Pathogenic	0.692	Likely Pathogenic	Likely Benign	0.125	Likely Benign	0.1241	0.2835											-1.45	Neutral	0.940	Possibly Damaging	0.360	Benign	4.19	Benign	0.09	Tolerated			3	0	-0.3	-9.01
c.543C>G	H181Q 2D AIThe SynGAP1 H181Q missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic vs two benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy tools therefore give a benign prediction from AlphaMissense‑Optimized, an inconclusive SGM Consensus, and an unavailable Foldetta result. Overall, the majority of predictions (six benign vs three pathogenic) indicate that the variant is most likely benign, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.505461	Disordered	0.439530	Uncertain	0.294	0.616	0.500							-9.577	Likely Pathogenic	0.692	Likely Pathogenic	Likely Benign	0.125	Likely Benign	0.1241	0.2835											-1.45	Neutral	0.940	Possibly Damaging	0.360	Benign	4.19	Benign	0.09	Tolerated			3	0	-0.3	-9.01
c.3449C>T	A1150V 2D AIThe SynGAP1 missense variant A1150V is listed in ClinVar (ID 589625.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33444484‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are SIFT and FATHMM. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is also benign. Foldetta, a protein‑folding stability method, did not provide a result for this variant. Overall, the majority of computational evidence indicates that A1150V is most likely benign, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.762850	Disordered	0.795712	Binding	0.371	0.831	0.625	Uncertain		1	6-33444484-C-T	3	1.86e-6	-3.648	Likely Benign	0.192	Likely Benign	Likely Benign	0.066	Likely Benign	0.1242	0.6335											-2.22	Neutral	0.114	Benign	0.055	Benign	2.32	Pathogenic	0.04	Affected	3.77	5	0	0	2.4	28.05
c.3579T>A	D1193E 2D AIThe SynGAP1 missense variant D1193E is predicted to be benign by the majority of in silico tools. Benign predictions come from REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT classifies the change as pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments further support a benign effect: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. ClinVar contains no entry for this variant, and it is absent from gnomAD, so there is no external evidence to contradict the computational predictions. Therefore, the variant is most likely benign, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.585406	Disordered	0.433390	Uncertain	0.807	0.600	0.375							-3.788	Likely Benign	0.237	Likely Benign	Likely Benign	0.307	Likely Benign	0.1242	0.3957											-1.09	Neutral	0.008	Benign	0.028	Benign	5.47	Benign	0.00	Affected			3	2	0.0	14.03
c.3579T>G	D1193E 2D AIThe SynGAP1 missense variant D1193E is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the only pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates a benign outcome. Foldetta results are not available, so they do not influence the assessment. Overall, the preponderance of evidence supports a benign classification for D1193E, and this conclusion is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.585406	Disordered	0.433390	Uncertain	0.807	0.600	0.375							-3.788	Likely Benign	0.237	Likely Benign	Likely Benign	0.307	Likely Benign	0.1242	0.3957											-1.09	Neutral	0.008	Benign	0.028	Benign	5.47	Benign	0.00	Affected			3	2	0.0	14.03
c.3661C>T	R1221W 2D AIThe SynGAP1 missense variant R1221W is listed in ClinVar with an uncertain significance (ClinVar ID 1050818.0) and is present in the gnomAD database (gnomAD ID 6‑33446653‑C‑T). Functional prediction tools show a split assessment: benign predictions come from REVEL and FATHMM, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy analyses further refine the picture: AlphaMissense‑Optimized classifies the variant as benign, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—deems it likely pathogenic. No Foldetta stability assessment is available for this residue. Overall, the majority of computational evidence points toward a pathogenic effect, which is consistent with the ClinVar designation of uncertain significance rather than a definitive benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.690604	Disordered	0.430363	Uncertain	0.906	0.539	0.375	Conflicting		3	6-33446653-C-T	1	6.20e-7	-10.938	Likely Pathogenic	0.651	Likely Pathogenic	Likely Benign	0.174	Likely Benign	0.1242	0.2585											-4.57	Deleterious	1.000	Probably Damaging	0.987	Probably Damaging	2.50	Benign	0.01	Affected	3.77	5	2	-3	3.6	30.03
c.3706C>A	Q1236K 2D AIThe SynGAP1 missense variant Q1236K is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized, whereas polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. Two tools—ESM1b and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it contains two benign and two uncertain calls, and Foldetta data are unavailable. Overall, the balance of evidence leans toward a benign classification, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.680603	Disordered	0.567914	Binding	0.883	0.537	0.125							-7.379	In-Between	0.512	Ambiguous	Likely Benign	0.142	Likely Benign	0.1242	0.2503											-1.64	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	2.73	Benign	0.02	Affected			1	1	-0.4	0.04
c.1598C>T	A533V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A533V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, Foldetta, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are SIFT and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta as benign, all supporting a non‑pathogenic interpretation. No prediction or folding‑stability result is missing or inconclusive. Based on the overall consensus of the available predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar evidence exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.179055	Structured	0.026324	Uncertain	0.843	0.393	0.000							-6.948	Likely Benign	0.148	Likely Benign	Likely Benign	0.170	Likely Benign	0.1243	0.6205		0.23	Likely Benign	0.0	0.51	Ambiguous	0.37	Likely Benign	0.25	Likely Benign	-2.41	Neutral	0.149	Benign	0.024	Benign	-1.28	Pathogenic	0.05	Affected			0	0	2.4	28.05
c.1765A>C	I589L 2D AIThe SynGAP1 missense variant I589L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only PROVEAN, whereas the remaining tools (REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus) all predict a pathogenic impact. High‑accuracy assessments further support a deleterious outcome: the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic”; AlphaMissense‑Optimized and Foldetta are inconclusive and therefore not considered evidence. Taken together, the preponderance of evidence points to a pathogenic effect for I589L. This conclusion is not contradicted by ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.018415	Structured	0.084536	Uncertain	0.927	0.214	0.000							-11.337	Likely Pathogenic	0.850	Likely Pathogenic	Ambiguous	0.728	Likely Pathogenic	0.1243	0.3430		0.95	Ambiguous	1.1	1.44	Ambiguous	1.20	Ambiguous	0.95	Ambiguous	-1.99	Neutral	0.955	Possibly Damaging	0.985	Probably Damaging	-1.76	Pathogenic	0.02	Affected			2	2	-0.7	0.00
c.1988T>A	F663Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F663Y is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and FATHMM. Those that predict a pathogenic effect comprise premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of tools and the SGM‑Consensus lean toward pathogenicity, while a minority suggest benign impact. Thus, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.056825	Structured	0.093963	Uncertain	0.944	0.355	0.000							-12.749	Likely Pathogenic	0.853	Likely Pathogenic	Ambiguous	0.424	Likely Benign	0.1243	0.1584		0.37	Likely Benign	0.1	0.19	Likely Benign	0.28	Likely Benign	1.03	Destabilizing	-2.99	Deleterious	0.984	Probably Damaging	0.913	Probably Damaging	3.11	Benign	0.05	Affected			7	3	-4.1	16.00
c.3004C>T	H1002Y 2D AIThe SynGAP1 missense variant H1002Y is not reported in ClinVar and is absent from gnomAD. Consensus from multiple in silico predictors indicates a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all score the change as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also classifies it as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The AlphaMissense‑Default tool remains uncertain, and no Foldetta stability assessment is available. High‑accuracy methods that are available—AlphaMissense‑Optimized and the SGM‑Consensus—both support a benign interpretation. Therefore, the variant is most likely benign based on the current predictive evidence, and this assessment does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.784345	Disordered	0.953758	Binding	0.285	0.900	0.500							-6.159	Likely Benign	0.489	Ambiguous	Likely Benign	0.181	Likely Benign	0.1243	0.4427											-1.85	Neutral	0.961	Probably Damaging	0.808	Possibly Damaging	2.74	Benign	0.14	Tolerated			0	2	1.9	26.03
c.1031G>T	G344V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G344V is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity uniformly indicate a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic, while the only inconclusive result is premPS, which is listed as uncertain. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic status; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports pathogenic. Consequently, the variant is most likely pathogenic, and this prediction is consistent with the absence of a ClinVar entry (no contradiction). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.264545	Structured	0.368110	Uncertain	0.913	0.485	0.250							-14.913	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.889	Likely Pathogenic	0.1244	0.4744		13.33	Destabilizing	1.5	14.51	Destabilizing	13.92	Destabilizing	0.53	Ambiguous	-7.97	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-0.48	Pathogenic	0.03	Affected			-1	-3	4.6	42.08
c.2693C>A	S898Y 2D AISynGAP1 missense variant S898Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Overall, the majority of tools and the consensus prediction indicate a pathogenic effect, and this conclusion does not contradict any ClinVar annotation because none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.690604	Disordered	0.426070	Uncertain	0.305	0.922	0.500							-5.927	Likely Benign	0.712	Likely Pathogenic	Likely Benign	0.182	Likely Benign	0.1244	0.6838											-2.69	Deleterious	0.998	Probably Damaging	0.959	Probably Damaging	2.44	Pathogenic	0.00	Affected			-3	-2	-0.5	76.10
c.3880G>A	A1294T 2D AIThe SynGAP1 missense variant A1294T is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33447928‑G‑A). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two benign vs two pathogenic votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy predictions show AlphaMissense‑Optimized as benign, while SGM Consensus and Foldetta remain unavailable. Overall, five tools predict pathogenicity versus four predicting benign, and the lack of ClinVar evidence does not contradict these findings. Thus, the variant is most likely pathogenic based on the current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.784345	Disordered	0.895011	Binding	0.565	0.806	0.625				6-33447928-G-A			-3.966	Likely Benign	0.093	Likely Benign	Likely Benign	0.290	Likely Benign	0.1244	0.5479											-3.04	Deleterious	0.999	Probably Damaging	0.989	Probably Damaging	2.18	Pathogenic	0.00	Affected	3.77	5	0	1	-2.5	30.03
c.1108G>T	G370C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G370C has no ClinVar entry and is not reported in gnomAD. Functional prediction tools fall into two groups: benign predictions come from premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from REVEL, FoldX, Rosetta, Foldetta, and FATHMM. ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. No prediction or stability result is missing. Overall, the majority of tools predict a benign effect, and the high‑accuracy consensus also leans benign, while only one high‑accuracy method (Foldetta) suggests pathogenicity. Thus, the variant is most likely benign based on the available predictions, and this assessment does not contradict any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.461924	Structured	0.434325	Uncertain	0.359	0.720	0.500							-7.071	In-Between	0.119	Likely Benign	Likely Benign	0.511	Likely Pathogenic	0.1245	0.4412		3.01	Destabilizing	2.1	2.03	Destabilizing	2.52	Destabilizing	0.29	Likely Benign	-1.00	Neutral	0.353	Benign	0.010	Benign	1.32	Pathogenic	0.06	Tolerated			-3	-3	2.9	46.09
c.170T>G	L57R 2D AIThe SynGAP1 missense variant L57R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which collectively classify the variant as likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default predict a pathogenic impact. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and Foldetta (combining FoldX‑MD and Rosetta outputs) is not available for this variant. Overall, the balance of evidence leans toward a benign interpretation, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.254060	Structured	0.481044	Uncertain	0.554	0.642	0.000							-6.034	Likely Benign	0.810	Likely Pathogenic	Ambiguous	0.213	Likely Benign	0.1245	0.0685											-1.55	Neutral	0.943	Possibly Damaging	0.944	Probably Damaging	3.91	Benign	0.00	Affected			-3	-2	-8.3	43.03
c.2864C>T	S955F 2D AISynGAP1 missense variant S955F is listed in ClinVar as uncertain and is present in gnomAD (ID 6‑33443416‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM; ESM1b is inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also returns benign, and Foldetta results are unavailable. Overall, the majority of high‑confidence predictions favor a benign impact, and this does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.984871	Disordered	0.945325	Binding	0.350	0.924	0.750	Conflicting		4	6-33443416-C-T	95	5.89e-5	-7.374	In-Between	0.176	Likely Benign	Likely Benign	0.093	Likely Benign	0.1246	0.4943											-1.73	Neutral	0.977	Probably Damaging	0.721	Possibly Damaging	2.32	Pathogenic	0.00	Affected	3.77	5	-3	-2	3.6	60.10
c.3013A>T	S1005C 2D AIThe SynGAP1 missense variant S1005C is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy consensus (SGM Consensus) derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN is inconclusive (two pathogenic vs. two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of standard predictors lean toward pathogenicity, while the single high‑accuracy tool that is available (AlphaMissense‑Optimized) predicts benign, and the consensus tool is inconclusive. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.812494	Disordered	0.936602	Binding	0.261	0.897	0.750							-8.519	Likely Pathogenic	0.640	Likely Pathogenic	Likely Benign	0.173	Likely Benign	0.1246	0.4492											-2.20	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.59	Benign	0.00	Affected			0	-1	3.3	16.06
c.110C>A	S37Y 2D AIThe SynGAP1 missense variant S37Y is listed in gnomAD (ID 6‑33423519‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default is uncertain, and Foldetta (FoldX‑MD/Rosetta stability assessment) has no available result. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta data is missing. Overall, the majority of evidence points to a benign effect. This conclusion is consistent with the absence of a ClinVar pathogenic classification, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.642678	Disordered	0.433492	Uncertain	0.317	0.806	0.500				6-33423519-C-A	1	6.20e-7	-4.447	Likely Benign	0.370	Ambiguous	Likely Benign	0.132	Likely Benign	0.1247	0.5256											-1.61	Neutral	0.880	Possibly Damaging	0.888	Possibly Damaging	3.90	Benign	0.00	Affected	4.32	1	-2	-3	-0.5	76.10
c.235A>C	N79H 2D AIThe SynGAP1 missense variant N79H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar classification because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.618285	Disordered	0.457064	Uncertain	0.290	0.876	0.375							-2.090	Likely Benign	0.110	Likely Benign	Likely Benign	0.045	Likely Benign	0.1247	0.4718											-0.72	Neutral	0.939	Possibly Damaging	0.114	Benign	4.16	Benign	0.00	Affected			2	1	0.3	23.04
c.3455A>T	E1152V 2D AIThe SynGAP1 missense variant E1152V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Pathogenic). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.741537	Disordered	0.811118	Binding	0.395	0.846	0.500							-3.304	Likely Benign	0.978	Likely Pathogenic	Likely Pathogenic	0.408	Likely Benign	0.1247	0.6384											-4.65	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	2.33	Pathogenic	0.00	Affected			-2	-2	7.7	-29.98
c.3622C>T	R1208W 2D AIThe SynGAP1 missense variant R1208W is recorded in gnomAD (variant ID 6‑33446614‑C‑T) but has no ClinVar entry. Prediction tools cluster into two groups: the single benign predictor REVEL, and a consensus of pathogenic predictions from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it “Likely Pathogenic.” No Foldetta stability result is available. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that R1208W is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.604312	Disordered	0.566942	Binding	0.899	0.569	0.375				6-33446614-C-T	1	6.20e-7	-12.124	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.192	Likely Benign	0.1247	0.2962											-5.53	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.47	Pathogenic	0.00	Affected	3.77	5	-3	2	3.6	30.03
c.1922C>T	S641L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S641L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it yields an equal split of benign and pathogenic calls. Overall, the majority of evidence points to a benign impact. This conclusion does not contradict any ClinVar annotation, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.125101	Structured	0.157322	Uncertain	0.786	0.270	0.000							-9.501	Likely Pathogenic	0.237	Likely Benign	Likely Benign	0.103	Likely Benign	0.1248	0.5376		0.33	Likely Benign	0.3	-0.14	Likely Benign	0.10	Likely Benign	0.32	Likely Benign	-4.33	Deleterious	0.115	Benign	0.014	Benign	3.39	Benign	0.07	Tolerated			-3	-2	4.6	26.08
c.1964T>A	L655Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L655Q is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate benign or likely benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity, while Rosetta remains inconclusive. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores benign, the SGM‑Consensus is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Overall, the majority of evidence supports a benign impact for L655Q, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.015344	Structured	0.268808	Uncertain	0.961	0.274	0.000	Uncertain		1				-5.278	Likely Benign	0.144	Likely Benign	Likely Benign	0.139	Likely Benign	0.1248	0.0972		-0.01	Likely Benign	0.0	0.69	Ambiguous	0.34	Likely Benign	-0.15	Likely Benign	0.61	Neutral	0.955	Possibly Damaging	0.602	Possibly Damaging	3.59	Benign	0.65	Tolerated	3.39	24	-2	-2	-7.3	14.97	229.9	-8.6	0.0	0.0	0.4	0.0						X		Potentially Benign	The iso-butyl side chain of Leu655, located on the surface of an α helix (res. Ser641-Glu666), is not involved in any interactions in the WT simulations. In the variant simulations, the carboxamide side chain of Gln655 dynamically interacts with neighboring residues (e.g., Glu651, Glu656, Arg544) on the protein surface, with no negative structural effects.
c.3116T>C	I1039T 2D AIThe SynGAP1 missense variant I1039T is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443668‑T‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM; the SGM‑Consensus score (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. Only AlphaMissense‑Default predicts a pathogenic effect. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM‑Consensus remains benign; a Foldetta stability analysis is not available. Overall, the majority of computational evidence supports a benign impact, and this is consistent with the ClinVar “Uncertain” classification, so there is no contradiction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.969315	Disordered	0.979204	Binding	0.292	0.806	0.625	Uncertain		1	6-33443668-T-C	12	7.43e-6	-2.465	Likely Benign	0.645	Likely Pathogenic	Likely Benign	0.193	Likely Benign	0.1248	0.2293											0.45	Neutral	0.004	Benign	0.008	Benign	2.75	Benign	0.10	Tolerated	3.77	5	-1	0	-5.2	-12.05
c.345G>C	Q115H 2D AIThe SynGAP1 missense variant Q115H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for Q115H, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.784345	Disordered	0.657256	Binding	0.327	0.878	0.750							-3.888	Likely Benign	0.277	Likely Benign	Likely Benign	0.156	Likely Benign	0.1248	0.3383											-0.99	Neutral	0.990	Probably Damaging	0.969	Probably Damaging	4.08	Benign	0.17	Tolerated			3	0	0.3	9.01
c.345G>T	Q115H 2D AIThe SynGAP1 missense variant Q115H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic effect. High‑accuracy assessments further support benignity: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence from multiple prediction algorithms and consensus methods points to a benign classification for Q115H, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.784345	Disordered	0.657256	Binding	0.327	0.878	0.750							-3.888	Likely Benign	0.277	Likely Benign	Likely Benign	0.156	Likely Benign	0.1248	0.3383											-0.99	Neutral	0.990	Probably Damaging	0.969	Probably Damaging	4.08	Benign	0.17	Tolerated			3	0	0.3	9.01
c.479T>A	L160Q 2D AIThe SynGAP1 missense variant L160Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.454136	Structured	0.526760	Binding	0.275	0.728	0.125							-16.626	Likely Pathogenic	0.973	Likely Pathogenic	Likely Pathogenic	0.227	Likely Benign	0.1248	0.1060											-2.83	Deleterious	0.700	Possibly Damaging	0.483	Possibly Damaging	3.87	Benign	0.00	Affected			-2	-2	-7.3	14.97
c.2330T>G	L777R 2D AIThe SynGAP1 missense variant L777R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.408655	Structured	0.876129	Binding	0.336	0.882	0.250							-6.084	Likely Benign	0.650	Likely Pathogenic	Likely Benign	0.227	Likely Benign	0.1249	0.0846											-2.20	Neutral	0.991	Probably Damaging	0.985	Probably Damaging	3.97	Benign	0.00	Affected			-3	-2	-8.3	43.03
c.3292A>T	S1098C 2D AIThe SynGAP1 missense variant S1098C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus likewise indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.973030	Binding	0.337	0.855	1.000							-6.553	Likely Benign	0.106	Likely Benign	Likely Benign	0.094	Likely Benign	0.1249	0.6233											-1.46	Neutral	0.938	Possibly Damaging	0.665	Possibly Damaging	2.65	Benign	0.12	Tolerated			0	-1	3.3	16.06
c.3516C>A	H1172Q 2D AIThe SynGAP1 missense variant H1172Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, SGM‑Consensus confirms Likely Benign, and Foldetta results are unavailable. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.626927	Disordered	0.673805	Binding	0.465	0.758	0.625							-2.169	Likely Benign	0.414	Ambiguous	Likely Benign	0.227	Likely Benign	0.1249	0.3557											-0.51	Neutral	0.451	Benign	0.265	Benign	5.47	Benign	0.39	Tolerated			3	0	-0.3	-9.01
c.3516C>G	H1172Q 2D AIThe SynGAP1 missense variant H1172Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, SGM‑Consensus confirms Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta) has no available result for this variant. Based on the collective predictions, H1172Q is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.626927	Disordered	0.673805	Binding	0.465	0.758	0.625							-2.169	Likely Benign	0.414	Ambiguous	Likely Benign	0.227	Likely Benign	0.1249	0.3557											-0.51	Neutral	0.451	Benign	0.265	Benign	5.47	Benign	0.39	Tolerated			3	0	-0.3	-9.01
c.767A>C	N256T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant N256T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split opinion: benign predictions come from Rosetta, Foldetta, premPS, and FATHMM, whereas pathogenic predictions are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). The high‑accuracy AlphaMissense‑Optimized model classifies the variant as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic, while the Foldetta stability assessment reports a benign effect. No prediction or stability result is missing or inconclusive. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.414856	Structured	0.234105	Uncertain	0.826	0.271	0.250							-12.212	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.819	Likely Pathogenic	0.1249	0.5848		0.88	Ambiguous	0.1	-0.18	Likely Benign	0.35	Likely Benign	0.49	Likely Benign	-5.25	Deleterious	0.997	Probably Damaging	0.980	Probably Damaging	5.85	Benign	0.01	Affected			0	0	2.8	-13.00
c.1150G>C	G384R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G384R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, premPS, PROVEAN, and AlphaMissense‑Optimized, whereas pathogenic calls are made by FoldX, Rosetta, Foldetta, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts benign, but SGM‑Consensus and Foldetta both predict pathogenic, with Foldetta integrating FoldX‑MD and Rosetta stability outputs. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.728858	Disordered	0.427831	Uncertain	0.323	0.934	0.750							-9.186	Likely Pathogenic	0.719	Likely Pathogenic	Likely Benign	0.475	Likely Benign	0.1250	0.4156		2.16	Destabilizing	0.4	5.06	Destabilizing	3.61	Destabilizing	0.25	Likely Benign	-0.96	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	1.32	Pathogenic	0.02	Affected			-3	-2	-4.1	99.14
c.3326T>A	L1109H 2D AIThe SynGAP1 missense variant L1109H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of computational evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.856457	Disordered	0.948334	Binding	0.343	0.893	0.875							-4.353	Likely Benign	0.237	Likely Benign	Likely Benign	0.134	Likely Benign	0.1250	0.1845											-0.56	Neutral	0.832	Possibly Damaging	0.499	Possibly Damaging	2.70	Benign	0.04	Affected			-2	-3	-7.0	23.98
c.385T>A	S129T 2D AIThe SynGAP1 missense variant S129T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions is that the variant is most likely benign, and this conclusion is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.517562	Disordered	0.713635	Binding	0.311	0.880	0.625							-4.296	Likely Benign	0.171	Likely Benign	Likely Benign	0.134	Likely Benign	0.1251	0.5794											0.12	Neutral	0.016	Benign	0.021	Benign	4.14	Benign	0.85	Tolerated			1	1	0.1	14.03
c.560T>A	L187Q 2D AIThe SynGAP1 missense variant L187Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all indicate likely pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as likely pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence from multiple in silico predictors points to a pathogenic effect for the SynGAP1 L187Q variant, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.465241	Structured	0.428046	Uncertain	0.367	0.625	0.375							-13.063	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.322	Likely Benign	0.1251	0.1060											-4.31	Deleterious	0.917	Possibly Damaging	0.548	Possibly Damaging	3.72	Benign	0.00	Affected			-2	-2	-7.3	14.97
c.1201C>T	R401W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R401W is listed in gnomAD (ID 6‑33438106‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions are returned by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). Only FATHMM predicts a benign outcome; all other tools are either pathogenic or inconclusive. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized classifies the variant as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic, while Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, yields an uncertain result. Taken together, the overwhelming majority of predictions support a pathogenic effect, and this conclusion is not contradicted by ClinVar data, which currently contains no classification for the variant. Based on the aggregate predictions, the variant is most likely pathogenic, and this is consistent with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.314870	Structured	0.424277	Uncertain	0.961	0.419	0.000				6-33438106-C-T	2	1.24e-6	-10.712	Likely Pathogenic	0.990	Likely Pathogenic	Likely Pathogenic	0.711	Likely Pathogenic	0.1252	0.3791		1.59	Ambiguous	0.2	1.04	Ambiguous	1.32	Ambiguous	0.73	Ambiguous	-7.34	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	5.40	Benign	0.00	Affected	3.38	27	-3	2	3.6	30.03
c.2060G>T	R687L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R687L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on benign include REVEL, SIFT, ESM1b, and FATHMM, while those that agree on pathogenic are AlphaMissense‑Default, PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The remaining tools—AlphaMissense‑Optimized, FoldX, Foldetta, and premPS—return uncertain or inconclusive results. High‑accuracy assessments are likewise inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a tie, and Foldetta is uncertain. Consequently, the evidence does not strongly support either benign or pathogenic classification. The variant is therefore most likely inconclusive, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.054297	Structured	0.191060	Uncertain	0.914	0.259	0.000							-6.925	Likely Benign	0.901	Likely Pathogenic	Ambiguous	0.448	Likely Benign	0.1252	0.3376		1.43	Ambiguous	0.3	0.05	Likely Benign	0.74	Ambiguous	0.83	Ambiguous	-5.76	Deleterious	1.000	Probably Damaging	0.987	Probably Damaging	3.90	Benign	0.10	Tolerated			-3	-2	8.3	-43.03
c.2474C>T	S825L 2D AIThe SynGAP1 missense variant S825L is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443026‑C‑T). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Pathogenic.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain,” and the Foldetta stability analysis is unavailable. Overall, the preponderance of evidence points to a pathogenic effect, which is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.675549	Disordered	0.618614	Binding	0.384	0.886	0.750	Uncertain		1	6-33443026-C-T	1	6.20e-7	-4.987	Likely Benign	0.910	Likely Pathogenic	Ambiguous	0.249	Likely Benign	0.1252	0.5747											-4.30	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	1.94	Pathogenic	0.01	Affected	3.77	5	-2	-3	4.6	26.08
c.2552C>G	P851R 2D AIThe SynGAP1 missense variant P851R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.526893	Binding	0.347	0.819	0.625							-4.154	Likely Benign	0.179	Likely Benign	Likely Benign	0.136	Likely Benign	0.1252	0.3873											-0.56	Neutral	0.999	Probably Damaging	0.997	Probably Damaging	4.22	Benign	0.09	Tolerated			0	-2	-2.9	59.07
c.2903G>T	G968V 2D AIThe SynGAP1 missense variant G968V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. The predictions do not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.978316	Disordered	0.961360	Binding	0.327	0.896	0.750							-6.152	Likely Benign	0.093	Likely Benign	Likely Benign	0.239	Likely Benign	0.1252	0.4036											-1.08	Neutral	0.918	Possibly Damaging	0.525	Possibly Damaging	4.19	Benign	0.11	Tolerated			-1	-3	4.6	42.08
c.3392C>G	P1131R 2D AIThe SynGAP1 P1131R missense variant has no ClinVar record and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta data are unavailable. With five benign versus four pathogenic calls and a benign result from the most accurate tool, the variant is most likely benign. This assessment does not contradict ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.919029	Disordered	0.855155	Binding	0.360	0.899	0.750							-3.792	Likely Benign	0.702	Likely Pathogenic	Likely Benign	0.416	Likely Benign	0.1252	0.4010											-2.58	Deleterious	0.918	Possibly Damaging	0.420	Benign	5.26	Benign	0.00	Affected			0	-2	-2.9	59.07
c.3580A>T	R1194W 2D AIThe SynGAP1 missense variant R1194W is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: benign predictions are limited to FATHMM, whereas the remaining methods—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM‑Consensus (majority vote) confirms a likely pathogenic status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence points to the variant being most likely pathogenic, with no ClinVar entry to contradict this assessment. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.685117	Disordered	0.425297	Uncertain	0.796	0.602	0.375							-9.583	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.514	Likely Pathogenic	0.1252	0.3162											-2.98	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	5.41	Benign	0.00	Affected			2	-3	3.6	30.03
c.950T>A	L317Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L317Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect. Benign predictions: none. Pathogenic predictions: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on these predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.106997	Structured	0.394031	Uncertain	0.874	0.240	0.125							-13.424	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	0.607	Likely Pathogenic	0.1252	0.1251		2.87	Destabilizing	0.2	2.47	Destabilizing	2.67	Destabilizing	1.61	Destabilizing	-5.52	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.75	Pathogenic	0.00	Affected			-2	-2	-7.3	14.97
c.988G>A	D330N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D330N missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict a pathogenic impact. High‑accuracy assessments further support a deleterious interpretation: the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic,” while AlphaMissense‑Optimized and Foldetta yield uncertain results and are treated as unavailable. No folding‑stability methods (FoldX, Rosetta, premPS) provide decisive evidence. Overall, the preponderance of pathogenic predictions strongly suggests that D330N is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.380708	Structured	0.360008	Uncertain	0.805	0.488	0.250							-12.993	Likely Pathogenic	0.909	Likely Pathogenic	Ambiguous	0.350	Likely Benign	0.1252	0.4263		1.61	Ambiguous	0.2	0.59	Ambiguous	1.10	Ambiguous	0.59	Ambiguous	-3.46	Deleterious	0.980	Probably Damaging	0.721	Possibly Damaging	1.01	Pathogenic	0.02	Affected			2	1	0.0	-0.98
c.2516A>T	K839M 2D AIThe SynGAP1 missense variant K839M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL indicates a benign likelihood, whereas the remaining predictors—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the change as pathogenic. The consensus score from the SGM framework, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Pathogenic.” High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts pathogenicity, and the SGM consensus also reports a likely pathogenic outcome. Foldetta, a protein‑folding stability method that combines FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion is consistent with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.642678	Disordered	0.611185	Binding	0.282	0.865	0.375							-13.688	Likely Pathogenic	0.979	Likely Pathogenic	Likely Pathogenic	0.241	Likely Benign	0.1253	0.4481											-3.54	Deleterious	1.000	Probably Damaging	0.983	Probably Damaging	2.40	Pathogenic	0.00	Affected			0	-1	5.8	3.02
c.1769G>A	S590N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S590N is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, while the majority of other in silico predictors (PolyPhen‑2 HumDiv/HumVar, SIFT, ESM1b, PROVEAN, premPS, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus) indicate a pathogenic or likely pathogenic impact. FoldX and Foldetta, which assess protein‑folding stability, return uncertain results and are therefore not considered evidence for either outcome. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of pathogenic predictions strongly suggests that S590N is most likely pathogenic, a conclusion that is consistent with the absence of ClinVar annotation and gnomAD data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.022667	Structured	0.088943	Uncertain	0.918	0.199	0.000							-15.149	Likely Pathogenic	0.957	Likely Pathogenic	Likely Pathogenic	0.411	Likely Benign	0.1254	0.4202		1.27	Ambiguous	0.1	2.10	Destabilizing	1.69	Ambiguous	1.48	Destabilizing	-2.96	Deleterious	0.921	Possibly Damaging	0.598	Possibly Damaging	3.14	Benign	0.01	Affected			1	1	-2.7	27.03
c.2153T>G	L718R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L718R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts pathogenicity. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.298791	Structured	0.438417	Uncertain	0.966	0.385	0.000							-16.119	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.484	Likely Benign	0.1254	0.0600		5.90	Destabilizing	0.2	5.05	Destabilizing	5.48	Destabilizing	2.57	Destabilizing	-5.69	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.28	Pathogenic	0.00	Affected			-3	-2	-8.3	43.03
c.3801G>A	M1267I 2D AIThe SynGAP1 missense variant M1267I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for M1267I. This conclusion is not contradicted by ClinVar status, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.429200	Structured	0.812047	Binding	0.847	0.614	0.000							-1.432	Likely Benign	0.936	Likely Pathogenic	Ambiguous	0.205	Likely Benign	0.1254	0.2741											-3.33	Deleterious	0.959	Probably Damaging	0.672	Possibly Damaging	2.33	Pathogenic	0.00	Affected			2	1	2.6	-18.03
c.3801G>C	M1267I 2D AIThe SynGAP1 missense variant M1267I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) remains Likely Pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for M1267I. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.429200	Structured	0.812047	Binding	0.847	0.614	0.000							-1.432	Likely Benign	0.936	Likely Pathogenic	Ambiguous	0.205	Likely Benign	0.1254	0.2741											-3.33	Deleterious	0.959	Probably Damaging	0.672	Possibly Damaging	2.33	Pathogenic	0.00	Affected			2	1	2.6	-18.03
c.3801G>T	M1267I 2D AIThe SynGAP1 missense variant M1267I is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) remains Likely Pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect for M1267I. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.429200	Structured	0.812047	Binding	0.847	0.614	0.000							-1.432	Likely Benign	0.936	Likely Pathogenic	Ambiguous	0.205	Likely Benign	0.1254	0.2741											-3.33	Deleterious	0.959	Probably Damaging	0.672	Possibly Damaging	2.33	Pathogenic	0.00	Affected			2	1	2.6	-18.03
c.1445T>G	L482R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L482R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate pathogenicity, while FoldX, Rosetta, and Foldetta return uncertain results. In a consensus framework, the SGM‑Consensus score is “Likely Pathogenic,” reflecting the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN. High‑accuracy assessments further support a damaging outcome: AlphaMissense‑Optimized predicts pathogenicity, SGM‑Consensus is Likely Pathogenic, and Foldetta remains inconclusive. Taken together, the overwhelming majority of evidence points to a pathogenic effect. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.426236	Uncertain	0.795	0.248	0.000							-14.684	Likely Pathogenic	0.976	Likely Pathogenic	Likely Pathogenic	0.878	Likely Pathogenic	0.1255	0.0679		0.74	Ambiguous	0.1	1.31	Ambiguous	1.03	Ambiguous	1.53	Destabilizing	-5.92	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	-1.27	Pathogenic	0.01	Affected			-3	-2	-8.3	43.03
c.2549G>T	G850V 2D AIThe SynGAP1 missense variant G850V is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools converge on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all indicate a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; no Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence points to a benign effect for G850V, and this conclusion is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.540897	Binding	0.312	0.820	0.500							-5.379	Likely Benign	0.081	Likely Benign	Likely Benign	0.213	Likely Benign	0.1255	0.4077											-1.74	Neutral	0.960	Probably Damaging	0.679	Possibly Damaging	4.21	Benign	0.02	Affected			-1	-3	4.6	42.08
c.26A>T	H9L 2D AIThe SynGAP1 missense variant H9L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.528099	Binding	0.394	0.916	0.750							-2.603	Likely Benign	0.135	Likely Benign	Likely Benign	0.151	Likely Benign	0.1255	0.6285											0.48	Neutral	0.024	Benign	0.002	Benign	4.25	Benign	0.00	Affected			-2	-3	7.0	-23.98
c.2722C>G	Q908E 2D AIThe SynGAP1 missense variant Q908E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign status: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect for Q908E, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.608892	Disordered	0.678728	Binding	0.275	0.917	0.250							-4.178	Likely Benign	0.271	Likely Benign	Likely Benign	0.139	Likely Benign	0.1255	0.1886											-1.14	Neutral	0.963	Probably Damaging	0.973	Probably Damaging	2.58	Benign	1.00	Tolerated			2	2	0.0	0.98
c.3901C>A	P1301T 2D AIThe SynGAP1 missense variant P1301T is reported in gnomAD (ID 6‑33451775‑C‑A) and has no ClinVar entry. All evaluated in silico predictors classify it as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments reinforce this benign prediction: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Based on the consensus of all available predictions, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.885064	Binding	0.447	0.841	0.875				6-33451775-C-A	1	6.20e-7	-4.945	Likely Benign	0.075	Likely Benign	Likely Benign	0.090	Likely Benign	0.1255	0.3312											0.34	Neutral	0.000	Benign	0.001	Benign	2.87	Benign	0.47	Tolerated	3.77	5	-1	0	0.9	3.99
c.1925A>T	K642M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K642M is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess the variant’s effect fall into two broad groups: benign predictions come from FoldX, premPS, and FATHMM; pathogenic predictions come from REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools give uncertain results: Rosetta and Foldetta. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely pathogenic. High‑accuracy assessments are as follows: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus also predicts pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. Overall, the preponderance of evidence from multiple independent predictors indicates that K642M is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.061840	Structured	0.181468	Uncertain	0.806	0.289	0.000							-13.557	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	0.510	Likely Pathogenic	0.1256	0.3589		0.43	Likely Benign	0.1	0.62	Ambiguous	0.53	Ambiguous	0.21	Likely Benign	-5.88	Deleterious	1.000	Probably Damaging	0.941	Probably Damaging	2.81	Benign	0.00	Affected			0	-1	5.8	3.02
c.3745A>T	R1249W 2D AIThe SynGAP1 missense variant R1249W is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL and AlphaMissense‑Optimized, whereas pathogenic predictions are returned by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized predicts benign, but the SGM‑Consensus (majority vote) is pathogenic, and no Foldetta stability data are available. Overall, the majority of evidence points toward a pathogenic effect, which is consistent with the SGM‑Consensus designation and contradicts the benign predictions from a minority of tools. Thus, the variant is most likely pathogenic, and this conclusion aligns with the lack of ClinVar annotation rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.745909	Disordered	0.366265	Uncertain	0.874	0.556	0.875							-9.841	Likely Pathogenic	0.477	Ambiguous	Likely Benign	0.209	Likely Benign	0.1256	0.2179											-6.18	Deleterious	1.000	Probably Damaging	0.990	Probably Damaging	1.68	Pathogenic	0.00	Affected			2	-3	3.6	30.03
c.926G>T	G309V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G309V is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity uniformly indicate a deleterious effect: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic, while premPS remains uncertain. No tool predicts a benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports likely pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also reports pathogenic. Consequently, the variant is most likely pathogenic, and this prediction is consistent with the absence of a ClinVar entry (no contradiction). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.275179	Structured	0.338439	Uncertain	0.882	0.342	0.125							-13.595	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.531	Likely Pathogenic	0.1256	0.3910		4.55	Destabilizing	0.5	3.61	Destabilizing	4.08	Destabilizing	0.76	Ambiguous	-8.27	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.67	Pathogenic	0.00	Affected			-1	-3	4.6	42.08
c.2963T>G	L988R 2D AIThe SynGAP1 missense variant L988R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.827927	Disordered	0.918781	Binding	0.360	0.913	0.750							-4.412	Likely Benign	0.681	Likely Pathogenic	Likely Benign	0.202	Likely Benign	0.1257	0.1088											-2.39	Neutral	0.954	Possibly Damaging	0.867	Possibly Damaging	2.69	Benign	0.00	Affected			-3	-2	-8.3	43.03
c.3062A>G	Q1021R 2D AIThe SynGAP1 missense variant Q1021R is catalogued in gnomAD (ID 6‑33443614‑A‑G) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves as “Likely Benign” (three benign votes versus one pathogenic). High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the majority of evidence points to a benign effect, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.899122	Disordered	0.979641	Binding	0.326	0.763	0.500				6-33443614-A-G	1	6.20e-7	-4.467	Likely Benign	0.770	Likely Pathogenic	Likely Benign	0.174	Likely Benign	0.1257	0.2405											-1.80	Neutral	0.985	Probably Damaging	0.982	Probably Damaging	2.61	Benign	0.03	Affected	3.77	5	1	1	-1.0	28.06
c.3752A>G	Q1251R 2D AIThe SynGAP1 missense variant Q1251R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) indicate a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.771762	Disordered	0.363872	Uncertain	0.869	0.551	0.875							-9.456	Likely Pathogenic	0.890	Likely Pathogenic	Ambiguous	0.236	Likely Benign	0.1257	0.1224											-2.92	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	2.50	Benign	0.00	Affected			1	1	-1.0	28.06
c.1327G>T	G443C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G443C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, premPS, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Pathogenic predictions come from PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The remaining tools are inconclusive: Foldetta is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” High‑accuracy assessments confirm this trend: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta remains uncertain. Overall, the consensus of the majority of evidence points to a benign impact for G443C, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.250310	Structured	0.258623	Uncertain	0.935	0.206	0.000							-4.308	Likely Benign	0.208	Likely Benign	Likely Benign	0.260	Likely Benign	0.1258	0.2782		-0.06	Likely Benign	0.0	-0.95	Ambiguous	-0.51	Ambiguous	-0.10	Likely Benign	-2.94	Deleterious	0.977	Probably Damaging	0.504	Possibly Damaging	3.37	Benign	0.16	Tolerated			-3	-3	2.9	46.09
c.2165G>A	S722N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S722N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that reach consensus classify the change as benign: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all predict a neutral effect. No tool predicts pathogenicity; the only inconclusive results come from premPS and AlphaMissense‑Default, which are treated as unavailable evidence. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports a benign outcome, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts a benign impact. Taken together, the evidence overwhelmingly supports a benign classification, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.468512	Structured	0.457186	Uncertain	0.950	0.431	0.375							-4.399	Likely Benign	0.379	Ambiguous	Likely Benign	0.051	Likely Benign	0.1258	0.3452		0.18	Likely Benign	0.1	0.15	Likely Benign	0.17	Likely Benign	0.79	Ambiguous	-0.91	Neutral	0.072	Benign	0.028	Benign	2.58	Benign	0.27	Tolerated			1	1	-2.7	27.03
c.3509G>C	S1170T 2D AIThe SynGAP1 missense variant S1170T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates “Likely Benign.” In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect for S1170T, and this conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.622677	Disordered	0.719138	Binding	0.417	0.767	0.500							-3.771	Likely Benign	0.163	Likely Benign	Likely Benign	0.338	Likely Benign	0.1258	0.5897											-1.13	Neutral	0.992	Probably Damaging	0.925	Probably Damaging	5.37	Benign	0.08	Tolerated			1	1	0.1	14.03
c.518T>G	L173R 2D AIThe SynGAP1 missense variant L173R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of consensus tools lean toward a benign interpretation, and there is no ClinVar evidence to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.534167	Disordered	0.491566	Uncertain	0.390	0.631	0.375							-9.524	Likely Pathogenic	0.904	Likely Pathogenic	Ambiguous	0.119	Likely Benign	0.1258	0.0761											-1.63	Neutral	0.561	Possibly Damaging	0.178	Benign	3.95	Benign	0.08	Tolerated			-3	-2	-8.3	43.03
c.850C>G	L284V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L284V missense variant has no ClinVar entry and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are Rosetta, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Predictions that are uncertain or inconclusive are FoldX, AlphaMissense‑Default, and Foldetta. High‑accuracy methods give a benign consensus: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors benign, while Foldetta remains uncertain. Overall, the balance of evidence leans toward a pathogenic effect, and this assessment does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.094817	Structured	0.371601	Uncertain	0.950	0.255	0.000							-6.726	Likely Benign	0.347	Ambiguous	Likely Benign	0.248	Likely Benign	0.1259	0.2456		1.65	Ambiguous	0.2	2.08	Destabilizing	1.87	Ambiguous	1.38	Destabilizing	-2.32	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	2.18	Pathogenic	0.03	Affected			2	1	0.4	-14.03
c.1817G>C	S606T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S606T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, and AlphaMissense‑Optimized, whereas a pathogenic consensus is reached by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Uncertain results come from Rosetta, premPS, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools predict pathogenicity, and the SGM Consensus supports this view, while the high‑accuracy methods give mixed results. Thus, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.041405	Structured	0.191720	Uncertain	0.875	0.247	0.000							-11.052	Likely Pathogenic	0.554	Ambiguous	Likely Benign	0.203	Likely Benign	0.1260	0.4513		0.06	Likely Benign	0.1	-0.91	Ambiguous	-0.43	Likely Benign	0.57	Ambiguous	-2.99	Deleterious	0.826	Possibly Damaging	0.933	Probably Damaging	3.34	Benign	0.03	Affected			1	1	0.1	14.03
c.3149G>T	G1050V 2D AIThe SynGAP1 missense variant G1050V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently contains no classification for G1050V. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.987317	Disordered	0.906802	Binding	0.370	0.928	0.875							-6.450	Likely Benign	0.108	Likely Benign	Likely Benign	0.066	Likely Benign	0.1260	0.3684											-0.83	Neutral	0.126	Benign	0.096	Benign	2.49	Pathogenic	0.13	Tolerated			-1	-3	4.6	42.08
c.3889A>T	R1297W 2D AIThe SynGAP1 missense variant R1297W is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta results are unavailable. Overall, the majority of evaluated predictors (five pathogenic vs. three benign) indicate a pathogenic impact. This conclusion is consistent with the lack of ClinVar reporting; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.859585	Disordered	0.895222	Binding	0.511	0.817	0.625							-6.039	Likely Benign	0.358	Ambiguous	Likely Benign	0.262	Likely Benign	0.1260	0.2587											-4.45	Deleterious	0.983	Probably Damaging	0.868	Possibly Damaging	2.44	Pathogenic	0.01	Affected			2	-3	3.6	30.03
c.1583C>G	P528R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P528R missense variant is not reported in ClinVar and is absent from gnomAD. No in silico predictor classifies it as benign; the following tools predict pathogenicity: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Predictions that are uncertain or inconclusive (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.225814	Structured	0.020396	Uncertain	0.909	0.403	0.000							-16.367	Likely Pathogenic	0.952	Likely Pathogenic	Ambiguous	0.615	Likely Pathogenic	0.1261	0.2543		0.76	Ambiguous	0.4	0.67	Ambiguous	0.72	Ambiguous	0.73	Ambiguous	-8.58	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.49	Pathogenic	0.01	Affected			0	-2	-2.9	59.07
c.2438T>G	L813R 2D AIThe SynGAP1 missense variant L813R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default predict a pathogenic outcome. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and Foldetta results are unavailable. Taken together, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently contains no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.411940	Structured	0.838481	Binding	0.292	0.905	0.250							-4.697	Likely Benign	0.786	Likely Pathogenic	Ambiguous	0.160	Likely Benign	0.1261	0.0947											-1.57	Neutral	0.999	Probably Damaging	0.985	Probably Damaging	2.68	Benign	0.11	Tolerated			-3	-2	-8.3	43.03
c.2494C>G	Q832E 2D AIThe SynGAP1 missense variant Q832E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags it as pathogenic, but this is the sole discordant call. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.720929	Disordered	0.619913	Binding	0.290	0.877	0.375							-3.024	Likely Benign	0.098	Likely Benign	Likely Benign	0.109	Likely Benign	0.1262	0.1897											-0.37	Neutral	0.652	Possibly Damaging	0.311	Benign	2.77	Benign	0.06	Tolerated			2	2	0.0	0.98
c.2581T>A	S861T 2D AIThe SynGAP1 missense variant S861T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. The high‑accuracy consensus, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), also reports a likely benign outcome. AlphaMissense‑Optimized likewise predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports a benign classification, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.557691	Disordered	0.540903	Binding	0.285	0.797	0.250							-4.462	Likely Benign	0.096	Likely Benign	Likely Benign	0.022	Likely Benign	0.1262	0.6245											-0.83	Neutral	0.043	Benign	0.026	Benign	3.99	Benign	0.14	Tolerated			1	1	0.1	14.03
c.2021C>A	T674N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T674N is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome; ESM1b is uncertain and does not influence the consensus. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized reports Benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts Benign. No contradictory evidence is present. **Based on the aggregate predictions, the variant is most likely benign, and this conclusion does not conflict with the ClinVar status.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.129801	Structured	0.109297	Uncertain	0.521	0.349	0.000							-7.839	In-Between	0.135	Likely Benign	Likely Benign	0.119	Likely Benign	0.1263	0.4979		-0.21	Likely Benign	0.0	0.15	Likely Benign	-0.03	Likely Benign	0.19	Likely Benign	-0.71	Neutral	0.958	Probably Damaging	0.671	Possibly Damaging	3.44	Benign	0.17	Tolerated			0	0	-2.8	13.00
c.2496G>C	Q832H 2D AIThe SynGAP1 missense variant Q832H is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign, while the single pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the consensus of the majority of tools and the high‑accuracy predictions point to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.720929	Disordered	0.619913	Binding	0.290	0.877	0.375							-3.322	Likely Benign	0.197	Likely Benign	Likely Benign	0.071	Likely Benign	0.1263	0.3230											-1.24	Neutral	0.064	Benign	0.038	Benign	2.76	Benign	0.03	Affected			3	0	0.3	9.01
c.2496G>T	Q832H 2D AIThe SynGAP1 missense variant Q832H is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign, while the single pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the consensus of the majority of tools and the high‑accuracy predictions point to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.720929	Disordered	0.619913	Binding	0.290	0.877	0.375							-3.322	Likely Benign	0.197	Likely Benign	Likely Benign	0.071	Likely Benign	0.1263	0.3230											-1.24	Neutral	0.064	Benign	0.038	Benign	2.76	Benign	0.03	Affected			3	0	0.3	9.01
c.2593G>A	A865T 2D AIThe SynGAP1 missense variant A865T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions is that the variant is most likely benign, and this conclusion does not contradict any ClinVar status, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.521092	Disordered	0.626222	Binding	0.271	0.788	0.250							-4.435	Likely Benign	0.078	Likely Benign	Likely Benign	0.026	Likely Benign	0.1263	0.6083											-0.84	Neutral	0.440	Benign	0.197	Benign	2.72	Benign	0.29	Tolerated			1	0	-2.5	30.03
c.2645G>A	G882E 2D AIThe SynGAP1 missense variant G882E is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑vs‑2 split; Foldetta results are unavailable. Overall, more tools (six) predict benign than pathogenic (three), and no ClinVar evidence contradicts this assessment. Thus, the variant is most likely benign based on current computational predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.690604	Disordered	0.632888	Binding	0.306	0.878	0.250							-4.246	Likely Benign	0.613	Likely Pathogenic	Likely Benign	0.079	Likely Benign	0.1263	0.3244											-1.16	Neutral	0.004	Benign	0.005	Benign	2.04	Pathogenic	0.01	Affected			0	-2	-3.1	72.06
c.3608A>G	H1203R 2D AIThe SynGAP1 missense variant H1203R is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts it as pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.618285	Disordered	0.527023	Binding	0.892	0.589	0.250							-3.355	Likely Benign	0.204	Likely Benign	Likely Benign	0.287	Likely Benign	0.1263	0.1178											-1.61	Neutral	0.473	Possibly Damaging	0.265	Benign	5.51	Benign	0.20	Tolerated			2	0	-1.3	19.05
c.1781T>A	F594Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F594Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are limited to Rosetta, which scores the substitution as benign. In contrast, the majority of tools predict a pathogenic impact: REVEL, SIFT, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, SGM‑Consensus, and premPS all classify the variant as pathogenic. FoldX and Foldetta are uncertain, and AlphaMissense‑Optimized is also uncertain, so these results are treated as unavailable. High‑accuracy assessments further support pathogenicity: the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic, while AlphaMissense‑Optimized and Foldetta remain inconclusive. Overall, the preponderance of evidence indicates that F594Y is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009187	Structured	0.120166	Uncertain	0.946	0.147	0.000							-13.692	Likely Pathogenic	0.935	Likely Pathogenic	Ambiguous	0.929	Likely Pathogenic	0.1264	0.0731		1.30	Ambiguous	0.2	0.41	Likely Benign	0.86	Ambiguous	1.21	Destabilizing	-2.99	Deleterious	0.993	Probably Damaging	0.976	Probably Damaging	-1.98	Pathogenic	0.01	Affected			7	3	-4.1	16.00
c.2542G>T	G848C 2D AIThe SynGAP1 missense variant G848C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of computational evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.563942	Binding	0.287	0.816	0.500							-6.987	Likely Benign	0.248	Likely Benign	Likely Benign	0.237	Likely Benign	0.1264	0.4400											-1.14	Neutral	0.998	Probably Damaging	0.922	Probably Damaging	2.55	Benign	0.01	Affected			-3	-3	2.9	46.09
c.2687G>T	G896V 2D AIThe SynGAP1 missense variant G896V is reported in gnomAD (6-33443239-G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Benign). Pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign outcome. Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect for G896V, and this conclusion is not contradicted by any ClinVar classification (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.675549	Disordered	0.412816	Uncertain	0.314	0.923	0.625				6-33443239-G-T	1	6.20e-7	-2.936	Likely Benign	0.285	Likely Benign	Likely Benign	0.165	Likely Benign	0.1264	0.4026											-1.96	Neutral	0.997	Probably Damaging	0.912	Probably Damaging	2.46	Pathogenic	0.30	Tolerated	4.32	4	-3	-1	4.6	42.08
c.3877G>A	D1293N 2D AIThe SynGAP1 missense variant D1293N is reported in gnomAD (6‑33447925‑G‑A) but has no ClinVar entry. Functional prediction tools split in a 5‑to‑4 ratio: benign calls come from REVEL, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic calls come from PROVEAN, polyPhen‑2 HumDiv, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive and Foldetta results are unavailable. Overall, the majority of evidence points toward a benign effect, and this conclusion does not contradict any ClinVar status because no ClinVar classification exists. Thus, the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.779859	Disordered	0.892346	Binding	0.569	0.801	0.625				6-33447925-G-A	5	3.22e-6	-3.983	Likely Benign	0.237	Likely Benign	Likely Benign	0.175	Likely Benign	0.1264	0.3421											-3.30	Deleterious	0.950	Possibly Damaging	0.414	Benign	2.33	Pathogenic	0.00	Affected	3.77	5	1	2	0.0	-0.98
c.106C>T	H36Y 2D AIThe SynGAP1 missense variant H36Y is listed in ClinVar with an uncertain significance (ClinVar ID 2089635.0) and is present in the gnomAD database (gnomAD ID 6‑33423515‑C‑T). Functional prediction tools largely agree that the substitution is benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report a benign effect. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled Likely Benign. No Foldetta stability prediction is available. Overall, the computational evidence overwhelmingly supports a benign classification, which is consistent with the ClinVar designation of uncertain significance rather than a pathogenic claim. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.433974	Uncertain	0.334	0.834	0.375	Uncertain		1	6-33423515-C-T	2	1.24e-6	-3.461	Likely Benign	0.139	Likely Benign	Likely Benign	0.023	Likely Benign	0.1265	0.5024											-1.03	Neutral	0.219	Benign	0.066	Benign	4.16	Benign	0.00	Affected	4.32	1	0	2	1.9	26.03
c.3215A>T	K1072M 2D AIThe SynGAP1 K1072M missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points toward a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign based on current predictive data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.922952	Disordered	0.984675	Binding	0.307	0.907	0.750							-2.821	Likely Benign	0.928	Likely Pathogenic	Ambiguous	0.144	Likely Benign	0.1266	0.4877											-1.37	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	3.88	Benign	0.02	Affected			0	-1	5.8	3.02
c.3428C>A	T1143K 2D AIThe SynGAP1 missense variant T1143K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, whereas the SGM‑Consensus (majority vote) supports a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact for T1143K, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.722918	Binding	0.275	0.837	1.000							-3.498	Likely Benign	0.811	Likely Pathogenic	Ambiguous	0.163	Likely Benign	0.1266	0.2936											-2.03	Neutral	0.986	Probably Damaging	0.895	Possibly Damaging	2.78	Benign	0.14	Tolerated			0	-1	-3.2	27.07
c.737T>G	L246R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L246R missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized reports pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.472492	Structured	0.302312	Uncertain	0.859	0.364	0.000							-13.849	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.925	Likely Pathogenic	0.1266	0.0600		3.94	Destabilizing	0.8	2.77	Destabilizing	3.36	Destabilizing	1.72	Destabilizing	-5.43	Deleterious	0.997	Probably Damaging	0.916	Probably Damaging	4.67	Benign	0.00	Affected			-3	-2	-8.3	43.03
c.1276A>C	N426H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N426H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, premPS, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. Predictions that are uncertain or inconclusive are FoldX and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign; and Foldetta also predicts a benign outcome. No prediction tool is missing or inconclusive in this set. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.042364	Structured	0.394941	Uncertain	0.959	0.287	0.000							-7.004	In-Between	0.248	Likely Benign	Likely Benign	0.237	Likely Benign	0.1267	0.3124		0.64	Ambiguous	0.0	-0.14	Likely Benign	0.25	Likely Benign	0.24	Likely Benign	-3.57	Deleterious	0.998	Probably Damaging	0.985	Probably Damaging	3.29	Benign	0.14	Tolerated			2	1	0.3	23.04
c.3137C>G	P1046R 2D AIThe SynGAP1 missense variant P1046R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all classify the change as benign or likely benign. Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized returns a benign prediction, and the SGM‑Consensus also indicates a likely benign status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.970265	Disordered	0.942366	Binding	0.364	0.898	0.750							-4.929	Likely Benign	0.222	Likely Benign	Likely Benign	0.077	Likely Benign	0.1267	0.3841											-1.79	Neutral	0.002	Benign	0.005	Benign	2.38	Pathogenic	0.07	Tolerated			0	-2	-2.9	59.07
c.436T>A	S146T 2D AIThe SynGAP1 missense variant S146T is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are SIFT, ESM1b, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is a tie (two pathogenic, two benign) and thus unavailable; Foldetta results are not provided. Overall, the majority of evidence (five benign vs. three pathogenic) supports a benign classification. This conclusion does not contradict ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.541878	Disordered	0.508612	Binding	0.349	0.837	0.625							-9.795	Likely Pathogenic	0.786	Likely Pathogenic	Ambiguous	0.113	Likely Benign	0.1267	0.5075											-2.09	Neutral	0.084	Benign	0.042	Benign	3.65	Benign	0.00	Affected			1	1	0.1	14.03
c.845G>T	C282F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C282F is not listed in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions are provided by REVEL and premPS, whereas the remaining 13 tools (FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all indicate pathogenicity. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is labeled Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports a pathogenic outcome. Taken together, the overwhelming majority of evidence points to a pathogenic impact for C282F. This conclusion is consistent with the absence of a ClinVar entry, which does not contradict the prediction. Thus, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.098513	Structured	0.348535	Uncertain	0.942	0.250	0.000							-13.288	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	0.430	Likely Benign	0.1267	0.3607		6.22	Destabilizing	1.4	2.38	Destabilizing	4.30	Destabilizing	0.42	Likely Benign	-10.11	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.65	Pathogenic	0.00	Affected			-4	-2	0.3	44.04
c.161A>C	N54T 2D AIThe SynGAP1 missense variant N54T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a benign impact, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.196879	Structured	0.464669	Uncertain	0.504	0.659	0.000							-5.808	Likely Benign	0.386	Ambiguous	Likely Benign	0.070	Likely Benign	0.1268	0.7498											-0.47	Neutral	0.659	Possibly Damaging	0.775	Possibly Damaging	4.20	Benign	0.00	Affected			0	0	2.8	-13.00
c.1808T>A	M603K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M603K is not reported in ClinVar and has no entries in gnomAD. Prediction tools largely agree on a deleterious effect: pathogenic calls come from REVEL, SGM Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized, while only FoldX reports a benign outcome. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is inconclusive. No other tools provide a clear benign signal. Consequently, the variant is most likely pathogenic, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.011342	Structured	0.197847	Uncertain	0.942	0.176	0.000							-15.561	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.933	Likely Pathogenic	0.1268	0.0488		0.17	Likely Benign	0.0	1.19	Ambiguous	0.68	Ambiguous	0.67	Ambiguous	-5.64	Deleterious	0.923	Possibly Damaging	0.922	Probably Damaging	-1.35	Pathogenic	0.00	Affected			0	-1	-5.8	-3.02
c.2627C>T	S876L 2D AISynGAP1 variant S876L is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), and SIFT. AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign effect; the SGM Consensus, derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive and therefore unavailable; Foldetta stability analysis is also unavailable. Overall, the majority of available predictions favor a benign impact, suggesting the variant is most likely benign. This conclusion does not conflict with the ClinVar uncertain status, which reflects the current lack of definitive evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.549308	Disordered	0.631130	Binding	0.280	0.872	0.250	Uncertain		2				-5.856	Likely Benign	0.489	Ambiguous	Likely Benign	0.249	Likely Benign	0.1268	0.6053											-3.56	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	2.57	Benign	0.05	Affected	3.77	5	-2	-3	4.6	26.08
c.3087G>C	Q1029H 2D AIThe SynGAP1 missense variant Q1029H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar classification, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.852992	Disordered	0.995643	Binding	0.375	0.734	0.500							-3.984	Likely Benign	0.308	Likely Benign	Likely Benign	0.041	Likely Benign	0.1268	0.4184											-0.83	Neutral	0.989	Probably Damaging	0.879	Possibly Damaging	2.74	Benign	0.15	Tolerated			3	0	0.3	9.01
c.3087G>T	Q1029H 2D AIThe SynGAP1 missense variant Q1029H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only two tools, polyPhen‑2 HumDiv and HumVar, predict a pathogenic outcome. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates likely benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the consensus of the available predictions indicates that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.852992	Disordered	0.995643	Binding	0.375	0.734	0.500							-3.984	Likely Benign	0.308	Likely Benign	Likely Benign	0.041	Likely Benign	0.1268	0.4184											-0.83	Neutral	0.989	Probably Damaging	0.879	Possibly Damaging	2.74	Benign	0.15	Tolerated			3	0	0.3	9.01
c.3347G>T	G1116V 2D AIThe SynGAP1 missense variant G1116V is reported in gnomAD (variant ID 6‑33443899‑G‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts it as pathogenic, creating a single discordant signal. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates the variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.889439	Disordered	0.873279	Binding	0.320	0.909	0.750				6-33443899-G-T			-6.426	Likely Benign	0.102	Likely Benign	Likely Benign	0.393	Likely Benign	0.1268	0.3494											-0.79	Neutral	0.626	Possibly Damaging	0.375	Benign	4.06	Benign	0.06	Tolerated	4.32	2	-3	-1	4.6	42.08
c.1826G>T	G609V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G609V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from premPS and AlphaMissense‑Optimized, whereas the remaining 10 tools (SGM Consensus, REVEL, FoldX, Rosetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM) all predict pathogenicity. High‑accuracy assessments further highlight the discordance: AlphaMissense‑Optimized reports a benign effect, whereas the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta outputs) both indicate pathogenicity. With the majority of evidence pointing to deleterious impact, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.179055	Structured	0.203786	Uncertain	0.851	0.252	0.000							-11.049	Likely Pathogenic	0.374	Ambiguous	Likely Benign	0.734	Likely Pathogenic	0.1269	0.3317		4.17	Destabilizing	0.3	3.77	Destabilizing	3.97	Destabilizing	0.34	Likely Benign	-4.47	Deleterious	0.974	Probably Damaging	0.818	Possibly Damaging	-1.48	Pathogenic	0.02	Affected			-1	-3	4.6	42.08
c.2708G>T	G903V 2D AIThe SynGAP1 missense variant G903V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts benign, while Foldetta results are unavailable. Overall, the balance of evidence (five benign predictions versus three pathogenic predictions, with no conflicting ClinVar annotation) indicates that the variant is most likely benign. This conclusion does not contradict any ClinVar status, as the variant is not currently catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.680603	Disordered	0.549818	Binding	0.291	0.917	0.375							-4.750	Likely Benign	0.491	Ambiguous	Likely Benign	0.168	Likely Benign	0.1269	0.4266											-1.93	Neutral	0.997	Probably Damaging	0.959	Probably Damaging	2.44	Pathogenic	0.95	Tolerated			-1	-3	4.6	42.08
c.3485C>G	P1162R 2D AIThe SynGAP1 missense variant P1162R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, the majority of predictions (5 pathogenic vs 4 benign) and the pathogenic call from AlphaMissense‑Optimized suggest the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.599170	Disordered	0.858809	Binding	0.366	0.823	0.375							-2.657	Likely Benign	0.977	Likely Pathogenic	Likely Pathogenic	0.208	Likely Benign	0.1269	0.3439											-2.68	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.70	Benign	0.14	Tolerated			0	-2	-2.9	59.07
c.3823C>T	R1275W 2D AIThe SynGAP1 missense variant R1275W is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33447871‑C‑T). Prediction tools that agree on a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas a majority (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b) predict a pathogenic impact; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a split vote (2 pathogenic, 1 benign, 1 uncertain). Foldetta, which would provide a protein‑folding stability estimate, has no available result for this variant. Overall, the balance of evidence leans toward a pathogenic classification, and this assessment does not contradict ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.648219	Disordered	0.790317	Binding	0.723	0.697	0.500				6-33447871-C-T	3	1.93e-6	-9.895	Likely Pathogenic	0.513	Ambiguous	Likely Benign	0.161	Likely Benign	0.1269	0.2372											-4.76	Deleterious	0.999	Probably Damaging	0.875	Possibly Damaging	2.51	Benign	0.00	Affected	3.77	5	-3	2	3.6	30.03
c.3847C>A	P1283T 2D AIThe SynGAP1 missense variant P1283T is catalogued in gnomAD (ID 6‑33447895‑C‑A) but has no ClinVar entry. Across a broad panel of in silico predictors, every tool reports a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool in the set predicts pathogenicity, so the pathogenic group is empty. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized returns a benign prediction, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence overwhelmingly supports a benign effect, and this is consistent with the absence of a ClinVar pathogenic classification. Therefore, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.762850	Disordered	0.819686	Binding	0.484	0.732	0.875				6-33447895-C-A			-4.781	Likely Benign	0.064	Likely Benign	Likely Benign	0.071	Likely Benign	0.1269	0.3784											-0.45	Neutral	0.451	Benign	0.193	Benign	2.76	Benign	0.11	Tolerated	3.77	5	-1	0	0.9	3.99
c.1739G>T	G580V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G580V is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess functional impact uniformly indicate a deleterious effect: REVEL, FoldX, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as pathogenic. The only inconclusive result is premPS, which is listed as uncertain. No tool predicts a benign effect. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenic. Based on the unanimous pathogenic predictions and the absence of any benign calls, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.025952	Uncertain	0.853	0.236	0.000							-13.705	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.750	Likely Pathogenic	0.1270	0.2909		4.10	Destabilizing	0.1	3.89	Destabilizing	4.00	Destabilizing	0.79	Ambiguous	-8.66	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	-1.18	Pathogenic	0.04	Affected			-1	-3	4.6	42.08
c.2249G>T	G750V 2D AIThe SynGAP1 missense variant G750V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs 2 pathogenic votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy predictions therefore show AlphaMissense‑Optimized as benign, while the remaining high‑confidence tools (PROVEAN, polyPhen‑2, SIFT, FATHMM) all indicate pathogenicity. Overall, the majority of evidence (five pathogenic vs four benign) points to a pathogenic effect. This conclusion is not contradicted by ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.618285	Disordered	0.646832	Binding	0.348	0.866	0.625							-4.512	Likely Benign	0.134	Likely Benign	Likely Benign	0.145	Likely Benign	0.1270	0.4212											-2.54	Deleterious	0.984	Probably Damaging	0.850	Possibly Damaging	2.45	Pathogenic	0.01	Affected			-1	-3	4.6	42.08
c.2686G>T	G896C 2D AIThe SynGAP1 missense variant G896C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. Thus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.675549	Disordered	0.412816	Uncertain	0.314	0.923	0.625							-5.607	Likely Benign	0.245	Likely Benign	Likely Benign	0.193	Likely Benign	0.1270	0.4369											-2.59	Deleterious	1.000	Probably Damaging	0.983	Probably Damaging	2.50	Benign	0.10	Tolerated			-3	-3	2.9	46.09
c.2750C>G	P917R 2D AIThe SynGAP1 missense variant P917R is listed in ClinVar with an “Uncertain” status and is present in gnomAD (gnomAD ID 6‑33443302‑C‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also as benign, while Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.599170	Disordered	0.863949	Binding	0.314	0.862	0.375	Uncertain		1	6-33443302-C-G	5	3.10e-6	-4.475	Likely Benign	0.363	Ambiguous	Likely Benign	0.142	Likely Benign	0.1270	0.3012											-1.70	Neutral	0.642	Possibly Damaging	0.316	Benign	2.68	Benign	0.00	Affected	3.77	5	-2	0	-2.9	59.07
c.2684G>A	S895N 2D AIThe SynGAP1 missense variant S895N is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM‑Consensus (majority vote) also leans benign. No Foldetta (protein‑folding stability) result is available, so it does not influence the assessment. Overall, the preponderance of predictions indicates the variant is most likely benign, which is consistent with its ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.788093	Disordered	0.414977	Uncertain	0.294	0.925	0.750	Uncertain		1				-6.399	Likely Benign	0.604	Likely Pathogenic	Likely Benign	0.118	Likely Benign	0.1271	0.4984											-0.85	Neutral	0.991	Probably Damaging	0.988	Probably Damaging	2.64	Benign	0.30	Tolerated	4.32	4	1	1	-2.7	27.03
c.323A>T	K108M 2D AIThe SynGAP1 K108M missense variant has no ClinVar record and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN), which collectively suggest a likely benign outcome. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized score is uncertain, and Foldetta stability analysis is unavailable. Overall, the balance of evidence leans toward a benign interpretation, and this assessment does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.626927	Disordered	0.673331	Binding	0.338	0.858	0.875							-3.863	Likely Benign	0.909	Likely Pathogenic	Ambiguous	0.216	Likely Benign	0.1271	0.4144											-1.64	Neutral	0.999	Probably Damaging	0.990	Probably Damaging	4.03	Benign	0.01	Affected			0	-1	5.8	3.02
c.3358G>T	G1120C 2D AIThe SynGAP1 missense variant G1120C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” No Foldetta stability result is available. Overall, the majority of evidence points to a benign impact for G1120C, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.871313	Disordered	0.804931	Binding	0.335	0.925	0.875							-9.324	Likely Pathogenic	0.112	Likely Benign	Likely Benign	0.311	Likely Benign	0.1271	0.4227											-1.32	Neutral	0.994	Probably Damaging	0.840	Possibly Damaging	3.60	Benign	0.03	Affected			-3	-3	2.9	46.09
c.3875T>A	L1292H 2D AIThe SynGAP1 missense variant L1292H is not reported in ClinVar (ClinVar status: None) but is present in gnomAD (ID 6‑33447923‑T‑A). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. The SGM Consensus, which takes a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs. 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the predictions are split, with a slight tilt toward pathogenicity (five pathogenic vs. four benign). Thus, the variant is most likely pathogenic based on the current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.779859	Disordered	0.882643	Binding	0.586	0.800	0.625				6-33447923-T-A			-5.692	Likely Benign	0.335	Likely Benign	Likely Benign	0.202	Likely Benign	0.1271	0.0649											-4.42	Deleterious	0.992	Probably Damaging	0.820	Possibly Damaging	2.46	Pathogenic	0.00	Affected	3.77	5	-3	-2	-7.0	23.98
c.752A>T	K251M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K251M missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, premPS, PROVEAN, and FATHMM. Those that predict pathogenicity are REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy assessment shows AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta predicts a benign effect. Overall, the evidence is evenly split between benign and pathogenic predictions, with the most reliable high‑accuracy tools leaning toward a benign outcome. Thus, the variant is most likely benign based on current predictions, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.447574	Structured	0.226632	Uncertain	0.758	0.312	0.125							-10.678	Likely Pathogenic	0.796	Likely Pathogenic	Ambiguous	0.751	Likely Pathogenic	0.1271	0.3475		0.14	Likely Benign	0.1	0.10	Likely Benign	0.12	Likely Benign	0.05	Likely Benign	-2.36	Neutral	0.999	Probably Damaging	0.970	Probably Damaging	5.73	Benign	0.05	Affected			0	-1	5.8	3.02
c.866T>A	M289K 2D 3DClick to see structure in 3D Viewer AISynGAP1 M289K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely pathogenic classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Because the majority of consensus and individual predictors lean toward pathogenicity, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status since none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.127496	Structured	0.403499	Uncertain	0.886	0.276	0.000							-12.192	Likely Pathogenic	0.738	Likely Pathogenic	Likely Benign	0.229	Likely Benign	0.1271	0.0879		0.36	Likely Benign	0.2	0.60	Ambiguous	0.48	Likely Benign	0.94	Ambiguous	-2.52	Deleterious	0.891	Possibly Damaging	0.492	Possibly Damaging	1.94	Pathogenic	0.12	Tolerated			0	-1	-5.8	-3.02
c.1154C>G	S385W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S385W is listed in ClinVar as Benign (ClinVar ID 218691.0) and is present in gnomAD (ID 6‑33438059‑C‑G). Functional prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, FATHMM, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM Consensus as Benign, and Foldetta as Uncertain. Taken together, the majority of evidence points to a benign impact, which aligns with the ClinVar classification and does not contradict it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.733139	Disordered	0.425480	Uncertain	0.341	0.925	0.750	Benign		1	6-33438059-C-G			-9.353	Likely Pathogenic	0.362	Ambiguous	Likely Benign	0.373	Likely Benign	0.1272	0.6670		0.53	Ambiguous	0.2	0.69	Ambiguous	0.61	Ambiguous	0.00	Likely Benign	-0.84	Neutral	0.986	Probably Damaging	0.968	Probably Damaging	4.63	Benign	0.00	Affected	4.32	3	-2	-3	-0.1	99.14	260.4	-71.2	0.5	1.3	0.7	0.4								Uncertain	Ser385 is located in the Gly-rich Ω loop (res. Pro364-Pro398) between two anti-parallel β sheet strands (res. Thr359-Pro364, res. Ala399-Ile411). Because the Ω loop is assumed to directly interact with the membrane, it moves arbitrarily throughout the WT solvent simulations. The Ω loop potentially plays a crucial role in the SynGAP-membrane complex association, stability, and dynamics. However, this aspect cannot be fully addressed through solvent simulations alone.Ω loops are known to play major roles in protein functions that require flexibility, and thus hydrophobic residues like tryptophan are rarely tolerated. Although no major negative structural effects are observed in the variant simulations, Trp385 may exert drastic effects on the SynGAP-membrane complex dynamics and stability. However, since the effects on Gly-rich Ω loop dynamics can only be studied through the SynGAP-membrane complex, no definite conclusions can be drawn.	10.1016/j.ajhg.2020.11.011
c.1315C>G	L439V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L439V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Tools that predict a pathogenic effect are FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar; premPS is inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of predictions (8 benign vs. 5 pathogenic) favor a benign classification, and this consensus does not contradict the absence of ClinVar evidence. Thus, based on current computational predictions, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.222385	Structured	0.281542	Uncertain	0.942	0.265	0.000							-6.340	Likely Benign	0.279	Likely Benign	Likely Benign	0.121	Likely Benign	0.1272	0.2628		2.34	Destabilizing	0.2	2.40	Destabilizing	2.37	Destabilizing	0.91	Ambiguous	-1.13	Neutral	0.976	Probably Damaging	0.941	Probably Damaging	3.36	Benign	0.12	Tolerated			2	1	0.4	-14.03
c.2291A>C	N764T 2D AIThe SynGAP1 missense variant N764T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. No Foldetta stability analysis is available, so it does not influence the assessment. Overall, the majority of computational evidence points to a benign impact, and this is consistent with the lack of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.380708	Structured	0.919527	Binding	0.305	0.861	0.250							-4.214	Likely Benign	0.449	Ambiguous	Likely Benign	0.071	Likely Benign	0.1272	0.5168											-1.57	Neutral	0.975	Probably Damaging	0.850	Possibly Damaging	2.63	Benign	0.05	Affected			0	0	2.8	-13.00
c.875C>T	A292V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A292V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact; premPS is uncertain and therefore not counted. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the overwhelming agreement among these predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.247041	Structured	0.362042	Uncertain	0.929	0.256	0.000							-11.170	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	0.430	Likely Benign	0.1272	0.6253		2.04	Destabilizing	0.5	4.60	Destabilizing	3.32	Destabilizing	0.85	Ambiguous	-3.68	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	1.75	Pathogenic	0.03	Affected			0	0	2.4	28.05
c.415A>T	S139C 2D AIThe SynGAP1 missense variant S139C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv and AlphaMissense‑Default predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority of the four high‑accuracy tools) also yields benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the S139C variant is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.553315	Disordered	0.600637	Binding	0.353	0.900	0.250							-6.964	Likely Benign	0.689	Likely Pathogenic	Likely Benign	0.087	Likely Benign	0.1273	0.4546											-2.43	Neutral	0.876	Possibly Damaging	0.319	Benign	4.07	Benign	0.06	Tolerated			0	-1	3.3	16.06
c.525A>C	Q175H 2D AIThe SynGAP1 missense variant Q175H has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are unavailable. Overall, the balance of evidence favors a benign classification, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.653063	Disordered	0.474689	Uncertain	0.367	0.618	0.375							-6.635	Likely Benign	0.824	Likely Pathogenic	Ambiguous	0.185	Likely Benign	0.1273	0.3411											-1.52	Neutral	0.875	Possibly Damaging	0.459	Possibly Damaging	4.09	Benign	0.10	Tolerated			3	0	0.3	9.01
c.525A>T	Q175H 2D AIThe SynGAP1 missense variant Q175H has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; no Foldetta stability data are available. Overall, the balance of evidence favors a benign classification, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.653063	Disordered	0.474689	Uncertain	0.367	0.618	0.375							-6.635	Likely Benign	0.824	Likely Pathogenic	Ambiguous	0.185	Likely Benign	0.1273	0.3411											-1.52	Neutral	0.875	Possibly Damaging	0.459	Possibly Damaging	4.09	Benign	0.10	Tolerated			3	0	0.3	9.01
c.2079T>A	H693Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H693Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL and FATHMM, while the remaining evaluated algorithms (premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) all predict pathogenicity. FoldX and Rosetta give uncertain stability changes, and Foldetta likewise reports no definitive effect. High‑accuracy assessments further support a deleterious interpretation: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains inconclusive. Overall, the preponderance of evidence from multiple pathogenic‑oriented predictors and the high‑accuracy consensus indicates that H693Q is most likely pathogenic, a conclusion that aligns with the lack of ClinVar annotation and gnomAD data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.073402	Structured	0.323991	Uncertain	0.964	0.260	0.000							-11.425	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.386	Likely Benign	0.1274	0.2955		0.92	Ambiguous	0.1	0.78	Ambiguous	0.85	Ambiguous	1.27	Destabilizing	-7.97	Deleterious	1.000	Probably Damaging	0.921	Probably Damaging	3.14	Benign	0.01	Affected			3	0	-0.3	-9.01
c.2079T>G	H693Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H693Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL and FATHMM, while the remaining evaluated algorithms (premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) all predict pathogenicity. FoldX and Rosetta give uncertain stability changes, and Foldetta likewise reports no definitive effect. High‑accuracy assessments further support a deleterious interpretation: AlphaMissense‑Optimized predicts pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains inconclusive. Overall, the preponderance of evidence from multiple pathogenic‑oriented predictors and the high‑accuracy consensus indicates that H693Q is most likely pathogenic, a conclusion that aligns with the lack of ClinVar annotation and gnomAD data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.073402	Structured	0.323991	Uncertain	0.964	0.260	0.000							-11.425	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.386	Likely Benign	0.1274	0.2955		0.92	Ambiguous	0.1	0.78	Ambiguous	0.85	Ambiguous	1.27	Destabilizing	-7.97	Deleterious	1.000	Probably Damaging	0.921	Probably Damaging	3.14	Benign	0.01	Affected			3	0	-0.3	-9.01
c.2300T>C	I767T 2D AIThe SynGAP1 missense variant I767T is listed in ClinVar (ID 1044161.0) with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags the variant as pathogenic, creating a single discordant prediction. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification, and AlphaMissense‑Optimized also reports benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, and this conclusion does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.321458	Structured	0.927771	Binding	0.369	0.872	0.125	Uncertain		1				-3.749	Likely Benign	0.252	Likely Benign	Likely Benign	0.138	Likely Benign	0.1274	0.1889											-0.78	Neutral	0.625	Possibly Damaging	0.249	Benign	4.12	Benign	0.46	Tolerated	3.64	6	0	-1	-5.2	-12.05
c.3152G>T	G1051V 2D AIThe SynGAP1 missense variant G1051V is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33443704‑G‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome, while ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a benign prediction (2 benign vs. 1 pathogenic, 1 uncertain). Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign effect for G1051V, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.987317	Disordered	0.900141	Binding	0.358	0.936	0.875				6-33443704-G-T	1	6.20e-7	-7.098	In-Between	0.102	Likely Benign	Likely Benign	0.460	Likely Benign	0.1274	0.3680											-0.62	Neutral	0.245	Benign	0.096	Benign	-0.74	Pathogenic	0.17	Tolerated	3.77	5	-3	-1	4.6	42.08
c.3272T>G	L1091R 2D AIThe SynGAP1 missense variant L1091R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of consensus tools (five pathogenic vs. three benign) suggest a pathogenic impact. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.924947	Disordered	0.984454	Binding	0.376	0.889	1.000							-3.662	Likely Benign	0.896	Likely Pathogenic	Ambiguous	0.191	Likely Benign	0.1274	0.1357											-1.51	Neutral	0.997	Probably Damaging	0.939	Probably Damaging	2.47	Pathogenic	0.02	Affected			-3	-2	-8.3	43.03
c.643G>T	G215C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G215C is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are premPS and FATHMM; those that agree on a pathogenic effect include SGM‑Consensus, REVEL, FoldX, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Rosetta gives an uncertain result and is listed separately. High‑accuracy methods all predict pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. Based on the overwhelming agreement among both general and high‑accuracy predictors, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.155435	Structured	0.382818	Uncertain	0.791	0.291	0.000							-12.295	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.869	Likely Pathogenic	0.1274	0.4640		2.39	Destabilizing	0.2	1.76	Ambiguous	2.08	Destabilizing	0.33	Likely Benign	-7.69	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	5.56	Benign	0.00	Affected			-3	-3	2.9	46.09
c.955G>A	A319T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A319T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, AlphaMissense‑Default, AlphaMissense‑Optimized, and polyPhen2_HumVar. Those that predict a pathogenic effect are polyPhen2_HumDiv and FATHMM. The remaining tools—FoldX, Rosetta, Foldetta, and ESM1b—return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as uncertain. Overall, the majority of reliable predictors classify the variant as benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.179055	Structured	0.410405	Uncertain	0.879	0.254	0.125							-7.841	In-Between	0.098	Likely Benign	Likely Benign	0.116	Likely Benign	0.1274	0.6083		0.55	Ambiguous	0.3	0.70	Ambiguous	0.63	Ambiguous	0.30	Likely Benign	-1.35	Neutral	0.775	Possibly Damaging	0.306	Benign	1.92	Pathogenic	0.09	Tolerated			1	0	-2.5	30.03
c.1234T>G	L412V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L412V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the remaining tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the preponderance of evidence, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.122885	Structured	0.331108	Uncertain	0.937	0.196	0.000							-11.726	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	0.231	Likely Benign	0.1275	0.3378		3.65	Destabilizing	0.0	3.52	Destabilizing	3.59	Destabilizing	1.54	Destabilizing	-2.76	Deleterious	0.995	Probably Damaging	0.970	Probably Damaging	3.25	Benign	0.01	Affected			2	1	0.4	-14.03
c.449T>G	L150R 2D AIThe SynGAP1 missense variant L150R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) all indicate pathogenicity. High‑accuracy assessments further support this: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus also reports it as Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of evidence from multiple in silico predictors and high‑accuracy tools points to a pathogenic effect for the SynGAP1 L150R variant, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.494003	Structured	0.505752	Binding	0.299	0.839	0.625							-14.879	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	0.290	Likely Benign	0.1275	0.0719											-3.16	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	3.67	Benign	0.00	Affected			-3	-2	-8.3	43.03
c.1983G>C	Q661H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q661H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, Rosetta, Foldetta, premPS, and FATHMM, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Uncertain calls are made by FoldX and AlphaMissense‑Optimized. High‑accuracy assessments indicate that the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, predicts a pathogenic effect, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign outcome. Overall, the balance of evidence leans toward a pathogenic interpretation, and this assessment does not conflict with ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.117089	Uncertain	0.924	0.309	0.000							-9.938	Likely Pathogenic	0.886	Likely Pathogenic	Ambiguous	0.282	Likely Benign	0.1276	0.3424		0.78	Ambiguous	0.1	0.07	Likely Benign	0.43	Likely Benign	0.09	Likely Benign	-3.78	Deleterious	0.993	Probably Damaging	0.819	Possibly Damaging	3.42	Benign	0.02	Affected			3	0	0.3	9.01
c.1983G>T	Q661H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q661H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, Rosetta, Foldetta, premPS, and FATHMM, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Uncertain calls are made by FoldX and AlphaMissense‑Optimized. High‑accuracy assessments indicate that the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, predicts a pathogenic effect, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign outcome. Overall, the balance of evidence leans toward a pathogenic interpretation, and this assessment does not conflict with ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.117089	Uncertain	0.924	0.309	0.000							-9.938	Likely Pathogenic	0.886	Likely Pathogenic	Ambiguous	0.282	Likely Benign	0.1276	0.3424		0.78	Ambiguous	0.1	0.07	Likely Benign	0.43	Likely Benign	0.09	Likely Benign	-3.78	Deleterious	0.993	Probably Damaging	0.819	Possibly Damaging	3.42	Benign	0.02	Affected			3	0	0.3	9.01
c.3727C>A	Q1243K 2D AIThe SynGAP1 missense variant Q1243K is reported in gnomAD (6‑33446719‑C‑A) and has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, polyPhen‑2 HumVar, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only polyPhen‑2 HumDiv predicts a pathogenic outcome; ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the collective predictions, the variant is most likely benign, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.545602	Disordered	0.433693	Uncertain	0.887	0.551	0.500				6-33446719-C-A	1	6.20e-7	-7.110	In-Between	0.230	Likely Benign	Likely Benign	0.050	Likely Benign	0.1276	0.2303											-1.39	Neutral	0.679	Possibly Damaging	0.446	Benign	2.72	Benign	0.08	Tolerated	3.77	5	1	1	-0.4	0.04
c.2489C>G	P830R 2D AIThe SynGAP1 missense variant P830R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also favors a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of reliable predictors and the high‑accuracy consensus indicate a benign impact. This conclusion is not contradicted by any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.590140	Disordered	0.618152	Binding	0.333	0.874	0.500							-5.919	Likely Benign	0.515	Ambiguous	Likely Benign	0.227	Likely Benign	0.1277	0.2984											-3.51	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.72	Benign	0.00	Affected			0	-2	-2.9	59.07
c.967C>G	L323V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L323V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, premPS, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) and pathogenic predictions (FoldX, Rosetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM). The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled Likely Benign. High‑accuracy assessments further refine the picture: AlphaMissense‑Optimized predicts benign; the SGM‑Consensus (majority of the four high‑accuracy tools) also indicates Likely Benign; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts pathogenic. Overall, the majority of evidence points to a benign effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.268042	Structured	0.428564	Uncertain	0.956	0.369	0.000							-3.483	Likely Benign	0.107	Likely Benign	Likely Benign	0.227	Likely Benign	0.1277	0.2656		2.18	Destabilizing	0.3	2.22	Destabilizing	2.20	Destabilizing	0.17	Likely Benign	0.19	Neutral	0.898	Possibly Damaging	0.472	Possibly Damaging	0.80	Pathogenic	0.80	Tolerated			2	1	0.4	-14.03
c.1652T>G	L551R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L551R is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a pathogenic effect include REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; the only tool with an uncertain outcome is FoldX. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenicity. Based on the concordant predictions from multiple independent algorithms and the absence of benign evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009977	Structured	0.006653	Uncertain	0.960	0.254	0.000							-15.420	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	0.949	Likely Pathogenic	0.1278	0.0530		1.81	Ambiguous	0.2	2.35	Destabilizing	2.08	Destabilizing	2.09	Destabilizing	-3.85	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.60	Pathogenic	0.01	Affected			-3	-2	-8.3	43.03
c.1730C>T	A577V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A577V is catalogued in gnomAD (ID 6‑33440782‑C‑T) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores benign; the SGM consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields benign; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also reports benign. No prediction or stability result is missing or inconclusive in these key analyses. Consequently, the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.113710	Structured	0.019074	Uncertain	0.913	0.239	0.000				6-33440782-C-T	2	1.24e-6	-4.265	Likely Benign	0.432	Ambiguous	Likely Benign	0.417	Likely Benign	0.1278	0.4790		0.69	Ambiguous	0.1	0.00	Likely Benign	0.35	Likely Benign	0.16	Likely Benign	-2.11	Neutral	0.997	Probably Damaging	0.976	Probably Damaging	-1.32	Pathogenic	0.26	Tolerated	3.37	34	0	0	2.4	28.05
c.2554G>T	G852C 2D AIThe SynGAP1 missense variant G852C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. ESM1b is uncertain, and Foldetta results are unavailable. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign,” and AlphaMissense‑Optimized independently predicts a benign outcome. With the majority of evidence pointing to a benign effect and no conflicting ClinVar annotation, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.733139	Disordered	0.506063	Binding	0.276	0.816	0.625							-7.462	In-Between	0.107	Likely Benign	Likely Benign	0.132	Likely Benign	0.1278	0.4808											-1.75	Neutral	0.992	Probably Damaging	0.873	Possibly Damaging	4.10	Benign	0.01	Affected			-3	-3	2.9	46.09
c.2774T>G	L925R 2D AIThe SynGAP1 missense variant L925R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only ESM1b, whereas the remaining tools—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized reports a pathogenic effect, and the SGM‑Consensus indicates a likely pathogenic classification. Foldetta results are not available for this variant. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.483068	Structured	0.977963	Binding	0.290	0.852	0.125							-2.340	Likely Benign	0.984	Likely Pathogenic	Likely Pathogenic	0.519	Likely Pathogenic	0.1278	0.1294											-4.54	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.28	Pathogenic	0.00	Affected			-3	-2	-8.3	43.03
c.3386T>A	L1129Q 2D AIThe SynGAP1 missense variant L1129Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of computational evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.876543	Binding	0.339	0.909	0.875							-3.684	Likely Benign	0.149	Likely Benign	Likely Benign	0.453	Likely Benign	0.1278	0.1436											-1.63	Neutral	0.846	Possibly Damaging	0.525	Possibly Damaging	5.49	Benign	0.00	Affected			-2	-2	-7.3	14.97
c.1504G>T	G502C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G502C lies in the GAP domain. ClinVar has no entry for this variant, and it is not reported in gnomAD. Prediction tools that agree on a benign effect include only premPS. The majority of tools predict a pathogenic effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. Tools with uncertain or inconclusive outputs are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (derived from a unanimous majority of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as uncertain. Overall, the preponderance of evidence points to a pathogenic impact for G502C, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.083462	Structured	0.340113	Uncertain	0.882	0.152	0.000							-12.086	Likely Pathogenic	0.907	Likely Pathogenic	Ambiguous	0.845	Likely Pathogenic	0.1279	0.2691		1.02	Ambiguous	0.5	1.55	Ambiguous	1.29	Ambiguous	0.30	Likely Benign	-8.65	Deleterious	1.000	Probably Damaging	0.988	Probably Damaging	-1.67	Pathogenic	0.00	Affected			-3	-3	2.9	46.09
c.2513A>C	N838T 2D AIThe SynGAP1 missense variant N838T is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, favors a benign outcome (2 benign vs. 1 pathogenic, with one uncertain). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. High‑accuracy predictions therefore point to a benign classification: AlphaMissense‑Optimized is benign, and the SGM Consensus is benign. Consequently, the variant is most likely benign based on current computational evidence, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.622677	Disordered	0.613320	Binding	0.276	0.861	0.250							-4.847	Likely Benign	0.373	Ambiguous	Likely Benign	0.091	Likely Benign	0.1279	0.5586											-2.59	Deleterious	0.997	Probably Damaging	0.992	Probably Damaging	2.69	Benign	0.12	Tolerated			0	0	2.8	-13.00
c.3065T>G	L1022R 2D AIThe SynGAP1 missense variant L1022R is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict the ClinVar status, which currently contains no classification for L1022R. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.859585	Disordered	0.986981	Binding	0.339	0.752	0.500							-2.875	Likely Benign	0.659	Likely Pathogenic	Likely Benign	0.183	Likely Benign	0.1279	0.1387											-1.96	Neutral	0.986	Probably Damaging	0.894	Possibly Damaging	2.51	Benign	0.01	Affected			-3	-2	-8.3	43.03
c.965C>T	A322V 2D AIThe SynGAP1 missense variant A322V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign; and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. No predictions or stability results are missing or inconclusive. Based on the overwhelming consensus of the available tools, the variant is most likely benign, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.175930	Structured	0.425745	Uncertain	0.938	0.334	0.000							-4.905	Likely Benign	0.121	Likely Benign	Likely Benign	0.052	Likely Benign	0.1279	0.6126		0.02	Likely Benign	1.0	-0.42	Likely Benign	-0.20	Likely Benign	0.19	Likely Benign	-1.63	Neutral	0.270	Benign	0.136	Benign	1.96	Pathogenic	0.22	Tolerated			0	0	2.4	28.05
c.193C>A	H65N 2D AIThe SynGAP1 missense variant H65N is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are AlphaMissense‑Default and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely benign; a Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this is consistent with the lack of ClinVar annotation. Thus, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.411940	Structured	0.476188	Uncertain	0.458	0.758	0.125							-2.788	Likely Benign	0.771	Likely Pathogenic	Likely Benign	0.038	Likely Benign	0.1280	0.2200											-1.42	Neutral	0.273	Benign	0.107	Benign	4.18	Benign	0.00	Affected			2	1	-0.3	-23.04
c.2690C>T	S897L 2D AIThe SynGAP1 missense variant S897L is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (derived from the same four high‑accuracy tools) also as benign. No Foldetta stability prediction is available for this variant. Overall, the majority of computational evidence points to a benign effect, and this conclusion does not conflict with the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.699094	Disordered	0.418474	Uncertain	0.292	0.928	0.500	Uncertain		1				-4.034	Likely Benign	0.299	Likely Benign	Likely Benign	0.028	Likely Benign	0.1280	0.5770											-1.71	Neutral	0.901	Possibly Damaging	0.636	Possibly Damaging	2.66	Benign	0.01	Affected			-3	-2	4.6	26.08
c.3631A>C	M1211L 2D AIThe SynGAP1 missense variant M1211L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as “Likely Benign.” In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict the variant to be pathogenic. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is “Likely Benign.” Foldetta results are not available, so they do not influence the overall assessment. Overall, the preponderance of evidence indicates that M1211L is most likely benign, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.585406	Disordered	0.578388	Binding	0.876	0.565	0.500							-2.552	Likely Benign	0.202	Likely Benign	Likely Benign	0.442	Likely Benign	0.1280	0.3547											-0.76	Neutral	0.856	Possibly Damaging	0.881	Possibly Damaging	5.45	Benign	0.14	Tolerated			4	2	1.9	-18.03
c.3631A>T	M1211L 2D AIThe SynGAP1 missense variant M1211L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as “Likely Benign.” In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict the variant to be pathogenic. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is “Likely Benign.” Foldetta results are not available, so they do not influence the overall assessment. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.585406	Disordered	0.578388	Binding	0.876	0.565	0.500							-2.552	Likely Benign	0.202	Likely Benign	Likely Benign	0.442	Likely Benign	0.1280	0.3547											-0.76	Neutral	0.856	Possibly Damaging	0.881	Possibly Damaging	5.45	Benign	0.14	Tolerated			4	2	1.9	-18.03
c.790C>G	L264V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L264V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are REVEL and AlphaMissense‑Optimized; all other evaluated algorithms (SGM‑Consensus, FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic or likely pathogenic outcome, while Rosetta remains uncertain. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) classifies the variant as Pathogenic. Overall, the preponderance of evidence points to a pathogenic effect for L264V, and this conclusion does not contradict the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.185198	Structured	0.323473	Uncertain	0.939	0.264	0.000							-10.621	Likely Pathogenic	0.630	Likely Pathogenic	Likely Benign	0.444	Likely Benign	0.1280	0.2289		2.55	Destabilizing	0.1	1.62	Ambiguous	2.09	Destabilizing	1.24	Destabilizing	-2.76	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	0.73	Pathogenic	0.01	Affected			2	1	0.4	-14.03
c.1247T>A	L416Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L416Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) all predict benign. Only two tools, polyPhen‑2 (HumDiv and HumVar), predict a pathogenic outcome. Stability‑based methods (FoldX, Rosetta, Foldetta, premPS) are inconclusive. High‑accuracy assessments reinforce the benign prediction: AlphaMissense‑Optimized is benign, the SGM‑Consensus is benign, and Foldetta remains uncertain. Overall, the evidence strongly supports a benign classification for this variant, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.104810	Structured	0.336105	Uncertain	0.935	0.227	0.000							-6.445	Likely Benign	0.234	Likely Benign	Likely Benign	0.187	Likely Benign	0.1281	0.0860		1.17	Ambiguous	0.1	0.54	Ambiguous	0.86	Ambiguous	0.88	Ambiguous	-1.07	Neutral	1.000	Probably Damaging	1.000	Probably Damaging	3.39	Benign	0.46	Tolerated			-2	-2	-7.3	14.97
c.1493T>A	M498K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M498K is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a deleterious effect: benign calls come only from polyPhen‑2 HumDiv and HumVar, whereas the remaining 15 tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) all predict pathogenicity. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized scores the variant as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) labels it likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts a destabilizing, pathogenic effect. Taken together, the overwhelming majority of evidence indicates that M498K is most likely pathogenic, and this conclusion is consistent with the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.092881	Structured	0.399612	Uncertain	0.932	0.158	0.000							-11.622	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	0.867	Likely Pathogenic	0.1281	0.0656		2.82	Destabilizing	0.1	2.86	Destabilizing	2.84	Destabilizing	1.79	Destabilizing	-4.53	Deleterious	0.287	Benign	0.120	Benign	-1.37	Pathogenic	0.00	Affected			0	-1	-5.8	-3.02
c.2993C>T	A998V 2D AIThe SynGAP1 missense variant A998V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus, SGM‑Consensus, classifies the variant as Likely Benign, and AlphaMissense‑Optimized also reports a benign prediction. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.759478	Disordered	0.951758	Binding	0.318	0.902	0.500							-4.795	Likely Benign	0.101	Likely Benign	Likely Benign	0.051	Likely Benign	0.1281	0.6147											-1.09	Neutral	0.245	Benign	0.138	Benign	4.09	Benign	0.00	Affected			0	0	2.4	28.05
c.3380G>T	G1127V 2D AIThe SynGAP1 missense variant G1127V is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33443932‑G‑T). All available in silico predictors classify the change as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool reports a pathogenic prediction. Grouping by agreement, the benign‑predicting tools comprise the entire set, while no pathogenic predictions exist. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” Foldetta results are unavailable. Overall, the variant is most likely benign, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.899122	Disordered	0.852422	Binding	0.344	0.915	0.875	Uncertain		1	6-33443932-G-T	1	6.69e-7	-6.097	Likely Benign	0.094	Likely Benign	Likely Benign	0.230	Likely Benign	0.1281	0.3669											-1.01	Neutral	0.004	Benign	0.005	Benign	4.81	Benign	0.17	Tolerated	4.32	4	-1	-3	4.6	42.08
c.3748C>G	Q1250E 2D AIThe SynGAP1 missense variant Q1250E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available. Overall, the majority of evidence points to a benign effect for Q1250E, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.759478	Disordered	0.360484	Uncertain	0.881	0.554	0.750							-3.860	Likely Benign	0.165	Likely Benign	Likely Benign	0.104	Likely Benign	0.1281	0.1130											-1.31	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	2.69	Benign	0.03	Affected			2	2	0.0	0.98
c.3751C>G	Q1251E 2D AIThe SynGAP1 missense variant Q1251E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized, whereas polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. Two tools, ESM1b and AlphaMissense‑Default, return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because it contains two uncertain and two benign calls, and Foldetta data are unavailable. Overall, the balance of evidence leans toward a benign interpretation, and this does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.771762	Disordered	0.363872	Uncertain	0.869	0.551	0.875							-7.836	In-Between	0.499	Ambiguous	Likely Benign	0.183	Likely Benign	0.1281	0.1266											-2.26	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	2.50	Benign	0.00	Affected			2	2	0.0	0.98
c.980T>G	L327R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L327R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that assess pathogenicity all agree that the variant is deleterious: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic. No tool predicts a benign effect. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a destabilizing, pathogenic effect. All available predictions are concordant and indicate a likely pathogenic impact. Thus, based on the current computational evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.335645	Structured	0.409189	Uncertain	0.939	0.490	0.000							-13.403	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.619	Likely Pathogenic	0.1281	0.1085		4.46	Destabilizing	0.3	4.75	Destabilizing	4.61	Destabilizing	1.95	Destabilizing	-5.28	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.52	Pathogenic	0.00	Affected			-3	-2	-8.3	43.03
c.1385A>T	K462M 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K462M missense variant is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, FATHMM, premPS, and the protein‑folding stability method Foldetta; pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score. Rosetta’s output is inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also pathogenic, while Foldetta indicates a benign effect on protein stability. No evidence from ClinVar contradicts these findings. Overall, the majority of predictive tools and the consensus score support a pathogenic classification, suggesting that K462M is most likely pathogenic rather than benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.297737	Uncertain	0.921	0.159	0.125							-12.837	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	0.475	Likely Benign	0.1282	0.3932		-0.23	Likely Benign	0.1	0.86	Ambiguous	0.32	Likely Benign	0.17	Likely Benign	-5.82	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.40	Benign	0.02	Affected			0	-1	5.8	3.02
c.3704T>A	M1235K 2D AIThe SynGAP1 missense variant M1235K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign effect. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the consensus of the majority of tools, including the high‑accuracy methods, supports a benign classification. This prediction is consistent with the lack of ClinVar evidence and does not contradict any existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.690604	Disordered	0.577958	Binding	0.872	0.532	0.125							-6.348	Likely Benign	0.269	Likely Benign	Likely Benign	0.109	Likely Benign	0.1282	0.0656											-2.37	Neutral	0.270	Benign	0.089	Benign	2.66	Benign	0.00	Affected			0	-1	-5.8	-3.02
c.2024A>C	N675T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N675T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and Foldetta. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. Uncertain results come from Rosetta and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split. No evidence contradicts the ClinVar status. Overall, the balance of evidence, especially from the high‑accuracy tools, indicates that the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.129801	Structured	0.111024	Uncertain	0.513	0.333	0.000							-10.636	Likely Pathogenic	0.208	Likely Benign	Likely Benign	0.258	Likely Benign	0.1283	0.7910		0.36	Likely Benign	0.3	-0.67	Ambiguous	-0.16	Likely Benign	0.56	Ambiguous	-4.63	Deleterious	0.991	Probably Damaging	0.710	Possibly Damaging	3.49	Benign	0.05	Affected			0	0	2.8	-13.00
c.3181G>T	G1061C 2D AIThe SynGAP1 missense variant G1061C is listed in ClinVar (ID 536997.0) with an “Uncertain” clinical significance and is present in gnomAD (variant ID 6‑33443733‑G‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; Foldetta results are not available. Overall, the majority of evidence (six benign vs. four pathogenic predictions) and the two high‑accuracy tools support a benign classification. This conclusion does not contradict the ClinVar status, which remains uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.978672	Disordered	0.926729	Binding	0.394	0.923	0.875	Conflicting		2	6-33443733-G-T	6	3.73e-6	-9.511	Likely Pathogenic	0.119	Likely Benign	Likely Benign	0.409	Likely Benign	0.1283	0.4227											-1.46	Neutral	0.938	Possibly Damaging	0.665	Possibly Damaging	3.97	Benign	0.00	Affected	4.32	2	-3	-3	2.9	46.09
c.3236G>C	S1079T 2D AIThe SynGAP1 missense variant S1079T is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores the variant as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence strongly suggests the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which currently has no entry for S1079T. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.983887	Binding	0.307	0.900	0.750							-3.225	Likely Benign	0.163	Likely Benign	Likely Benign	0.023	Likely Benign	0.1283	0.5920											-1.28	Neutral	0.001	Benign	0.003	Benign	3.91	Benign	0.00	Affected			1	1	0.1	14.03
c.3323G>A	S1108N 2D AIThe SynGAP1 missense variant S1108N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for S1108N, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.852992	Disordered	0.949221	Binding	0.324	0.886	0.875							-6.488	Likely Benign	0.250	Likely Benign	Likely Benign	0.070	Likely Benign	0.1283	0.3952											-2.02	Neutral	0.611	Possibly Damaging	0.239	Benign	2.47	Pathogenic	0.06	Tolerated			1	1	-2.7	27.03
c.1886T>A	V629D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V629D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all return pathogenic or likely pathogenic calls, whereas only FATHMM predicts a benign outcome. High‑accuracy assessments reinforce this trend: AlphaMissense‑Optimized indicates pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) predicts pathogenic. No predictions are missing or inconclusive. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.040537	Structured	0.034796	Uncertain	0.970	0.236	0.000							-17.143	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.713	Likely Pathogenic	0.1284	0.0541		3.85	Destabilizing	0.1	3.82	Destabilizing	3.84	Destabilizing	2.17	Destabilizing	-6.37	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.06	Benign	0.00	Affected			-2	-3	-7.7	15.96
c.2213G>A	S738N 2D AIThe SynGAP1 missense variant S738N is reported in ClinVar as having no entry and is not present in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus, derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a benign majority vote, matching the SGM‑Consensus label of “Likely Benign.” Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, and this assessment is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.812494	Disordered	0.441162	Uncertain	0.284	0.827	0.875							-5.005	Likely Benign	0.075	Likely Benign	Likely Benign	0.059	Likely Benign	0.1284	0.3251											-0.53	Neutral	0.425	Benign	0.233	Benign	2.69	Benign	0.02	Affected			1	1	-2.7	27.03
c.2366C>A	P789Q 2D AIThe SynGAP1 P789Q missense change is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) favors pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not contradict the ClinVar status, which currently has no classification for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.963420	Disordered	0.541575	Binding	0.398	0.903	0.750							-5.191	Likely Benign	0.465	Ambiguous	Likely Benign	0.235	Likely Benign	0.1284	0.3215											-4.53	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.03	Pathogenic	0.00	Affected			0	-1	-1.9	31.01
c.3755A>G	Q1252R 2D AIThe SynGAP1 missense variant Q1252R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: REVEL scores the variant as benign, whereas PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict pathogenicity. Grouping by consensus, the majority of tools (seven) support a pathogenic effect, while only one tool (REVEL) indicates benign. High‑accuracy assessments further support a deleterious impact: the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic; AlphaMissense‑Optimized remains uncertain, and Foldetta data are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus result, the variant is most likely pathogenic. This conclusion aligns with the lack of ClinVar annotation and gnomAD absence, and there is no contradiction with ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.759478	Disordered	0.371411	Uncertain	0.850	0.544	0.875							-11.890	Likely Pathogenic	0.913	Likely Pathogenic	Ambiguous	0.249	Likely Benign	0.1284	0.0854											-3.26	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	2.00	Pathogenic	0.00	Affected			1	1	-1.0	28.06
c.704C>G	S235C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S235C is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FATHMM and Rosetta, whereas a majority of tools (REVEL, SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) predict a pathogenic impact. Results from high‑accuracy methods are mixed: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta is uncertain. Because the uncertain predictions are treated as unavailable, the overall evidence still favors pathogenicity. Thus, the variant is most likely pathogenic, and this assessment does not contradict the current ClinVar status, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.250310	Structured	0.319150	Uncertain	0.743	0.331	0.000							-11.350	Likely Pathogenic	0.800	Likely Pathogenic	Ambiguous	0.878	Likely Pathogenic	0.1284	0.6015		1.74	Ambiguous	0.1	0.42	Likely Benign	1.08	Ambiguous	0.76	Ambiguous	-4.24	Deleterious	0.977	Probably Damaging	0.620	Possibly Damaging	5.45	Benign	0.00	Affected			0	-1	3.3	16.06
c.1021G>T	G341C 2D AIThe SynGAP1 missense variant G341C has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include FoldX, Foldetta, premPS, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (likely benign). Tools that predict a pathogenic effect are REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; Rosetta remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Based on the overall consensus of the available predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.356642	Structured	0.431164	Uncertain	0.745	0.479	0.250							-6.156	Likely Benign	0.190	Likely Benign	Likely Benign	0.501	Likely Pathogenic	0.1285	0.3650		0.42	Likely Benign	1.2	-0.92	Ambiguous	-0.25	Likely Benign	0.24	Likely Benign	-2.40	Neutral	0.997	Probably Damaging	0.870	Possibly Damaging	0.34	Pathogenic	0.01	Affected			-3	-3	2.9	46.09
c.2435C>G	P812R 2D AIThe SynGAP1 P812R missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default; AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, the majority of standard predictors indicate a pathogenic impact, while the most accurate tools provide no definitive evidence. Thus, the variant is most likely pathogenic, and this assessment does not contradict any existing ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.414856	Structured	0.842442	Binding	0.388	0.901	0.125							-6.784	Likely Benign	0.799	Likely Pathogenic	Ambiguous	0.222	Likely Benign	0.1285	0.3525											-2.70	Deleterious	0.999	Probably Damaging	0.985	Probably Damaging	2.77	Benign	0.01	Affected			0	-2	-2.9	59.07
c.2663C>T	A888V 2D AIThe SynGAP1 missense variant A888V is catalogued in gnomAD (ID 6‑33443215‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign or tolerated outcomes, while the single pathogenic signal comes from SIFT. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates a benign likelihood. Foldetta results are unavailable, so they do not influence the assessment. Overall, the preponderance of evidence points to a benign impact for A888V, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.784345	Disordered	0.575860	Binding	0.352	0.928	0.625				6-33443215-C-T	1	6.20e-7	-4.241	Likely Benign	0.106	Likely Benign	Likely Benign	0.034	Likely Benign	0.1285	0.7056											-0.91	Neutral	0.000	Benign	0.001	Benign	2.78	Benign	0.00	Affected	4.32	4	0	0	2.4	28.05
c.3257C>A	P1086Q 2D AIThe SynGAP1 missense variant P1086Q is not reported in ClinVar (ClinVar status: None) but is present in gnomAD (ID 6‑33443809‑C‑A). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two pathogenic vs. two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions (five pathogenic vs. four benign) indicate that the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.849326	Disordered	0.977190	Binding	0.393	0.885	1.000				6-33443809-C-A			-4.668	Likely Benign	0.652	Likely Pathogenic	Likely Benign	0.185	Likely Benign	0.1285	0.4784											-2.92	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.77	Benign	0.00	Affected	3.77	5	-1	0	-1.9	31.01
c.2306T>G	L769R 2D AIThe SynGAP1 missense variant L769R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is unavailable for this variant. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.411940	Structured	0.928432	Binding	0.367	0.883	0.250							-6.245	Likely Benign	0.493	Ambiguous	Likely Benign	0.206	Likely Benign	0.1286	0.0702											-1.66	Neutral	0.003	Benign	0.006	Benign	3.91	Benign	0.00	Affected			-3	-2	-8.3	43.03
c.3875T>G	L1292R 2D AIThe SynGAP1 missense variant L1292R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (2 benign vs 2 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, five tools predict pathogenicity while four predict benignity, giving a slight tilt toward a pathogenic interpretation. This prediction does not contradict ClinVar status, as the variant has not yet been classified in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.779859	Disordered	0.882643	Binding	0.586	0.800	0.625							-4.249	Likely Benign	0.238	Likely Benign	Likely Benign	0.223	Likely Benign	0.1286	0.0849											-4.34	Deleterious	0.971	Probably Damaging	0.773	Possibly Damaging	2.46	Pathogenic	0.00	Affected			-3	-2	-8.3	43.03
c.1187G>T	G396V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G396V is catalogued in gnomAD (6‑33438092‑G‑T) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are FoldX, Rosetta, Foldetta, and PROVEAN. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely benign, while Foldetta (combining FoldX‑MD and Rosetta outputs) indicates a pathogenic effect. Overall, the majority of predictions lean toward a benign impact, and this consensus does not contradict any ClinVar status (none reported). Thus, based on the available computational evidence, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.414856	Structured	0.394626	Uncertain	0.640	0.584	0.500				6-33438092-G-T	6	3.72e-6	-5.663	Likely Benign	0.120	Likely Benign	Likely Benign	0.332	Likely Benign	0.1287	0.4337		3.49	Destabilizing	1.7	5.28	Destabilizing	4.39	Destabilizing	0.34	Likely Benign	-2.56	Deleterious	0.062	Benign	0.014	Benign	3.90	Benign	0.24	Tolerated	3.41	15	-3	-1	4.6	42.08
c.1670C>G	S557C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S557C is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include premPS and AlphaMissense‑Optimized, whereas the majority of other in silico predictors (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) classify the change as pathogenic. FoldX, Rosetta, and Foldetta provide uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, while the SGM‑Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—predicts pathogenic. Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains uncertain. Overall, the preponderance of evidence from multiple pathogenic predictors and the SGM‑Consensus suggests the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because the variant is not yet reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.028107	Structured	0.010261	Uncertain	0.924	0.215	0.000							-9.845	Likely Pathogenic	0.577	Likely Pathogenic	Likely Benign	0.923	Likely Pathogenic	0.1287	0.5678		1.43	Ambiguous	0.1	1.74	Ambiguous	1.59	Ambiguous	0.49	Likely Benign	-4.52	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	-1.77	Pathogenic	0.00	Affected			0	-1	3.3	16.06
c.1211C>T	A404V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A404V missense variant is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33438116‑C‑T). Prediction tools that agree on a benign effect include REVEL, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN and ESM1b. Four tools (FoldX, Rosetta, AlphaMissense‑Default, Foldetta) give uncertain or inconclusive results. High‑accuracy methods give mixed evidence: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic, and Foldetta remains uncertain. Overall, the majority of predictions lean toward a benign impact, though a key consensus method suggests pathogenicity, leaving the variant’s effect unresolved. **The variant is most likely benign based on the prevailing predictions, and this assessment does not contradict ClinVar status, as no ClinVar classification exists.** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.232838	Structured	0.415505	Uncertain	0.965	0.355	0.000				6-33438116-C-T	1	6.20e-7	-8.219	Likely Pathogenic	0.343	Ambiguous	Likely Benign	0.118	Likely Benign	0.1288	0.6842		0.56	Ambiguous	0.3	-1.55	Ambiguous	-0.50	Ambiguous	-0.05	Likely Benign	-2.96	Deleterious	0.345	Benign	0.018	Benign	4.20	Benign	0.47	Tolerated	3.38	28	0	0	2.4	28.05
c.1262C>A	A421E 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A421E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM, whereas pathogenic calls are made by ESM1b, PROVEAN, AlphaMissense‑Default, AlphaMissense‑Optimized, Rosetta, premPS, and the SGM‑Consensus score (Likely Pathogenic). Stability‑based methods give mixed results: FoldX is uncertain, Foldetta is uncertain, and Rosetta alone predicts pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta remains uncertain. Overall, the majority of evidence, including the high‑accuracy tools, points to a pathogenic impact for A421E, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.404927	Uncertain	0.965	0.257	0.000							-11.993	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.233	Likely Benign	0.1288	0.1830		0.63	Ambiguous	0.2	2.07	Destabilizing	1.35	Ambiguous	1.30	Destabilizing	-4.24	Deleterious	0.368	Benign	0.144	Benign	3.44	Benign	0.14	Tolerated			0	-1	-5.3	58.04
c.1858T>A	S620T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S620T has no ClinVar entry and is not reported in gnomAD. Prediction tools that classify it as benign include Foldetta, premPS, PROVEAN, SIFT, AlphaMissense‑Optimized, and Rosetta. Those that predict pathogenicity are SGM‑Consensus, REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized labeling the variant as benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicating likely pathogenic, and Foldetta predicting benign stability. No prediction or folding result is missing or inconclusive. Overall, the majority of tools lean toward a pathogenic effect, and this assessment does not contradict the ClinVar status, which is currently unclassified. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.139895	Structured	0.100377	Uncertain	0.936	0.219	0.000							-9.171	Likely Pathogenic	0.660	Likely Pathogenic	Likely Benign	0.551	Likely Pathogenic	0.1288	0.5199		0.52	Ambiguous	0.1	-0.40	Likely Benign	0.06	Likely Benign	0.30	Likely Benign	-1.99	Neutral	0.896	Possibly Damaging	0.933	Probably Damaging	-1.25	Pathogenic	0.14	Tolerated			1	1	0.1	14.03
c.1891C>A	Q631K 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q631K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from FoldX, Foldetta, and FATHMM, while pathogenic predictions arise from REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score. Uncertain or inconclusive results are reported by Rosetta, premPS, and AlphaMissense‑Optimized. High‑accuracy methods give a mixed picture: Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a benign effect; the SGM‑Consensus, a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic outcome; AlphaMissense‑Optimized remains uncertain. Overall, the majority of evidence points toward a pathogenic impact, and this assessment does not conflict with the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.038963	Uncertain	0.948	0.230	0.000							-15.194	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous	0.596	Likely Pathogenic	0.1288	0.2157		-0.37	Likely Benign	0.1	1.13	Ambiguous	0.38	Likely Benign	0.88	Ambiguous	-3.98	Deleterious	0.958	Probably Damaging	0.931	Probably Damaging	2.79	Benign	0.01	Affected			1	1	-0.4	0.04
c.2462G>A	C821Y 2D AIThe SynGAP1 missense variant C821Y is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 vs 2), and Foldetta results are unavailable. Overall, seven tools support pathogenicity while three support benignity, and no high‑accuracy consensus contradicts this trend. Therefore, the variant is most likely pathogenic based on the available predictions, and this assessment does not conflict with the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.745909	Disordered	0.672821	Binding	0.351	0.883	0.750							-1.007	Likely Benign	0.982	Likely Pathogenic	Likely Pathogenic	0.342	Likely Benign	0.1288	0.3187											-3.11	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.66	Benign	0.01	Affected			0	-2	-3.8	60.04
c.460A>T	S154C 2D AIThe SynGAP1 missense variant S154C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. ESM1b is uncertain, and Foldetta results are unavailable. The high‑accuracy consensus (SGM‑Consensus) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. With the majority of evidence pointing to a benign outcome and no conflicting ClinVar annotation, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.505461	Disordered	0.508330	Binding	0.284	0.795	0.500							-7.728	In-Between	0.244	Likely Benign	Likely Benign	0.100	Likely Benign	0.1288	0.5042											-1.83	Neutral	0.997	Probably Damaging	0.841	Possibly Damaging	4.01	Benign	0.04	Affected			0	-1	3.3	16.06
c.1394T>A	L465H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L465H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect. Benign predictions: none. Pathogenic predictions: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts pathogenic. Based on the consensus of all available predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.346032	Structured	0.319240	Uncertain	0.956	0.202	0.000							-16.751	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.764	Likely Pathogenic	0.1289	0.1089		3.15	Destabilizing	0.4	2.29	Destabilizing	2.72	Destabilizing	2.54	Destabilizing	-6.96	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.29	Pathogenic	0.00	Affected			-2	-3	-7.0	23.98
c.1184G>T	G395V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G395V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while only FoldX and SIFT predict pathogenic. The SGM‑Consensus score, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and the Foldetta stability analysis is uncertain. Taken together, the preponderance of evidence points to a benign impact for G395V, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.513880	Disordered	0.396199	Uncertain	0.474	0.601	0.500							-5.617	Likely Benign	0.125	Likely Benign	Likely Benign	0.288	Likely Benign	0.1290	0.4183		2.83	Destabilizing	0.7	-0.37	Likely Benign	1.23	Ambiguous	0.08	Likely Benign	-1.49	Neutral	0.000	Benign	0.000	Benign	4.21	Benign	0.03	Affected			-1	-3	4.6	42.08
c.2393C>A	P798Q 2D AIThe SynGAP1 missense variant P798Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect for P798Q, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.871313	Disordered	0.492709	Uncertain	0.426	0.899	0.875							-5.944	Likely Benign	0.074	Likely Benign	Likely Benign	0.068	Likely Benign	0.1290	0.3864											-0.53	Neutral	0.988	Probably Damaging	0.780	Possibly Damaging	4.25	Benign	0.00	Affected			0	-1	-1.9	31.01
c.3914C>A	T1305K 2D AIThe SynGAP1 missense variant T1305K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores the variant as benign, and the SGM Consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also indicates a likely benign effect. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact for T1305K, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.791621	Disordered	0.894658	Binding	0.390	0.873	0.875							-4.289	Likely Benign	0.299	Likely Benign	Likely Benign	0.164	Likely Benign	0.1290	0.3532											-1.33	Neutral	0.027	Benign	0.042	Benign	2.77	Benign	0.01	Affected			0	-1	-3.2	27.07
c.2557G>T	G853C 2D AIThe SynGAP1 G853C missense variant has no ClinVar record and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. ESM1b is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.657645	Disordered	0.496246	Uncertain	0.284	0.815	0.625							-7.021	In-Between	0.096	Likely Benign	Likely Benign	0.120	Likely Benign	0.1292	0.4944											-1.65	Neutral	0.992	Probably Damaging	0.873	Possibly Damaging	4.10	Benign	0.00	Affected			-3	-3	2.9	46.09
c.2635G>A	A879T 2D AIThe SynGAP1 missense variant A879T is reported in gnomAD (6-33443187‑G‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict it to be pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign. No Foldetta stability analysis is available, so it does not influence the overall assessment. Taken together, the majority of evidence points to a benign impact for A879T, and this conclusion is not contradicted by any ClinVar classification (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.608892	Disordered	0.622695	Binding	0.277	0.874	0.250				6-33443187-G-A	3	1.86e-6	-5.161	Likely Benign	0.090	Likely Benign	Likely Benign	0.042	Likely Benign	0.1292	0.6754											-0.98	Neutral	0.872	Possibly Damaging	0.580	Possibly Damaging	2.66	Benign	0.19	Tolerated	3.77	5	0	1	-2.5	30.03
c.32G>T	G11V 2D AIThe SynGAP1 missense variant G11V is reported in gnomAD (variant ID 6‑33420296‑G‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the preponderance of evidence from both general and high‑accuracy tools indicates that G11V is most likely benign, and this conclusion is not contradicted by any ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.444081	Structured	0.501027	Binding	0.348	0.915	0.375				6-33420296-G-T			-4.079	Likely Benign	0.160	Likely Benign	Likely Benign	0.146	Likely Benign	0.1292	0.4522											-0.38	Neutral	0.668	Possibly Damaging	0.049	Benign	3.93	Benign	0.00	Affected	4.32	1	-3	-1	4.6	42.08
c.631A>T	S211C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S211C is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, AlphaMissense‑Optimized, and premPS, whereas a separate group predicts pathogenicity: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Two tools (Rosetta and AlphaMissense‑Default) return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Because the consensus of the most reliable predictors is split (two benign, one pathogenic) and the overall tool distribution is evenly divided, the variant’s impact remains ambiguous. Based on the available predictions, the variant is most likely benign, and this assessment does not contradict the ClinVar status, which currently has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.209395	Structured	0.389893	Uncertain	0.846	0.300	0.125							-10.567	Likely Pathogenic	0.547	Ambiguous	Likely Benign	0.263	Likely Benign	0.1292	0.5638		0.28	Likely Benign	0.1	0.63	Ambiguous	0.46	Likely Benign	0.11	Likely Benign	-4.14	Deleterious	0.999	Probably Damaging	0.908	Possibly Damaging	3.89	Benign	0.01	Affected			0	-1	3.3	16.06
c.2392C>A	P798T 2D AIThe SynGAP1 missense variant P798T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence—including the high‑accuracy tools—points to a benign effect for P798T, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.871313	Disordered	0.492709	Uncertain	0.426	0.899	0.875							-5.926	Likely Benign	0.062	Likely Benign	Likely Benign	0.039	Likely Benign	0.1293	0.4854											-0.38	Neutral	0.901	Possibly Damaging	0.534	Possibly Damaging	4.24	Benign	0.00	Affected			0	-1	0.9	3.99
c.262G>A	V88M 2D AISynGAP1 missense variant V88M is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools show a split: benign predictions come from REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. AlphaMissense‑Optimized alone predicts Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points toward a benign effect, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.552910	Binding	0.323	0.870	0.500							-5.851	Likely Benign	0.987	Likely Pathogenic	Likely Pathogenic	0.103	Likely Benign	0.1293	0.4463											-0.91	Neutral	0.975	Probably Damaging	0.171	Benign	3.67	Benign	0.00	Affected			2	1	-2.3	32.06
c.2724G>C	Q908H 2D AIThe SynGAP1 missense variant Q908H is listed in ClinVar (ID 436926.0) with an “Uncertain” status and is present in gnomAD (variant ID 6‑33443276‑G‑C). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This consensus does not contradict the ClinVar “Uncertain” classification, which remains inconclusive. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.608892	Disordered	0.678728	Binding	0.275	0.917	0.250	Conflicting		4	6-33443276-G-C	1	6.20e-7	-4.658	Likely Benign	0.311	Likely Benign	Likely Benign	0.112	Likely Benign	0.1293	0.3597											-0.74	Neutral	0.996	Probably Damaging	0.995	Probably Damaging	2.58	Benign	0.05	Affected	3.77	5	3	0	0.3	9.01
c.2724G>T	Q908H 2D AIThe SynGAP1 missense variant Q908H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all classify the change as benign or likely benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized reports benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely benign. Foldetta results are not available. Overall, the majority of evidence points to a benign effect for Q908H, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.608892	Disordered	0.678728	Binding	0.275	0.917	0.250							-4.658	Likely Benign	0.311	Likely Benign	Likely Benign	0.110	Likely Benign	0.1293	0.3597											-0.74	Neutral	0.996	Probably Damaging	0.995	Probably Damaging	2.58	Benign	0.05	Affected	3.77	5	3	0	0.3	9.01
c.3896T>A	L1299H 2D AIThe SynGAP1 missense variant L1299H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.771762	Disordered	0.896323	Binding	0.398	0.832	0.750							-4.586	Likely Benign	0.300	Likely Benign	Likely Benign	0.317	Likely Benign	0.1293	0.1273											-3.83	Deleterious	0.992	Probably Damaging	0.750	Possibly Damaging	2.67	Benign	0.00	Affected			-2	-3	-7.0	23.98
c.2902G>T	G968C 2D AIThe SynGAP1 missense variant G968C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.978316	Disordered	0.961360	Binding	0.327	0.896	0.750							-8.441	Likely Pathogenic	0.117	Likely Benign	Likely Benign	0.170	Likely Benign	0.1294	0.4768											-0.99	Neutral	0.992	Probably Damaging	0.820	Possibly Damaging	4.12	Benign	0.07	Tolerated			-3	-3	2.9	46.09
c.3008G>T	S1003I 2D AIThe SynGAP1 missense variant S1003I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The high‑accuracy consensus methods give mixed results: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two pathogenic, two benign votes); and Foldetta (combining FoldX‑MD and Rosetta) has no available output. Based on the overall distribution of predictions, the variant is most likely pathogenic. This assessment does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.834292	Disordered	0.947349	Binding	0.272	0.901	0.625							-8.952	Likely Pathogenic	0.954	Likely Pathogenic	Ambiguous	0.189	Likely Benign	0.1294	0.5735											-2.31	Neutral	0.999	Probably Damaging	0.998	Probably Damaging	2.50	Benign	0.00	Affected			-1	-2	5.3	26.08
c.3646C>G	L1216V 2D AIThe SynGAP1 missense variant L1216V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two agreement groups: benign predictions come from REVEL and PROVEAN, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. Two tools—ESM1b and AlphaMissense‑Optimized—return uncertain results. High‑accuracy assessment further shows that AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.580690	Disordered	0.504713	Binding	0.863	0.563	0.250							-7.842	In-Between	0.861	Likely Pathogenic	Ambiguous	0.126	Likely Benign	0.1294	0.1883											-2.26	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	2.20	Pathogenic	0.00	Affected			2	1	0.4	-14.03
c.3890G>T	R1297M 2D AIThe SynGAP1 missense variant R1297M is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact. This conclusion is not contradicted by ClinVar status, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.859585	Disordered	0.895222	Binding	0.511	0.817	0.625							-4.286	Likely Benign	0.383	Ambiguous	Likely Benign	0.139	Likely Benign	0.1294	0.2449											-3.00	Deleterious	0.938	Possibly Damaging	0.690	Possibly Damaging	2.45	Pathogenic	0.02	Affected			0	-1	6.4	-24.99
c.569G>C	S190T 2D AIThe SynGAP1 missense variant S190T is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, SGM‑Consensus confirms Likely Benign, and Foldetta results are unavailable. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.422041	Structured	0.428613	Uncertain	0.338	0.615	0.250							-6.870	Likely Benign	0.408	Ambiguous	Likely Benign	0.114	Likely Benign	0.1294	0.6920											-1.31	Neutral	0.608	Possibly Damaging	0.108	Benign	4.08	Benign	0.20	Tolerated			1	1	0.1	14.03
c.1144G>A	G382R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G382R is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include premPS, PROVEAN, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts a benign change, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta stability outputs) both predict pathogenicity. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.728858	Disordered	0.429690	Uncertain	0.315	0.951	0.750							-8.997	Likely Pathogenic	0.654	Likely Pathogenic	Likely Benign	0.595	Likely Pathogenic	0.1295	0.4346		4.53	Destabilizing	1.6	8.03	Destabilizing	6.28	Destabilizing	0.23	Likely Benign	-0.95	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	1.32	Pathogenic	0.02	Affected			-3	-2	-4.1	99.14
c.1144G>C	G382R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G382R is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include premPS, PROVEAN, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts a benign change, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta stability outputs) both predict pathogenicity. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.728858	Disordered	0.429690	Uncertain	0.315	0.951	0.750							-8.997	Likely Pathogenic	0.654	Likely Pathogenic	Likely Benign	0.570	Likely Pathogenic	0.1295	0.4346		4.53	Destabilizing	1.6	8.03	Destabilizing	6.28	Destabilizing	0.23	Likely Benign	-0.95	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	1.32	Pathogenic	0.02	Affected			-3	-2	-4.1	99.14
c.1147G>A	G383R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G383R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, FATHMM, AlphaMissense‑Optimized, and polyPhen2_HumVar. Tools that agree on a pathogenic effect are FoldX, Rosetta, Foldetta, polyPhen2_HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, Foldetta predicts a pathogenic outcome, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two pathogenic vs. two benign). Overall, the majority of predictions lean toward pathogenicity, and this does not contradict the ClinVar status, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.728858	Disordered	0.429104	Uncertain	0.296	0.949	0.750							-9.067	Likely Pathogenic	0.660	Likely Pathogenic	Likely Benign	0.449	Likely Benign	0.1295	0.3741		4.03	Destabilizing	2.3	3.36	Destabilizing	3.70	Destabilizing	0.29	Likely Benign	-0.84	Neutral	0.498	Possibly Damaging	0.119	Benign	4.10	Benign	0.00	Affected			-3	-2	-4.1	99.14
c.1147G>C	G383R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G383R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, FATHMM, AlphaMissense‑Optimized, and polyPhen2_HumVar. Tools that agree on a pathogenic effect are FoldX, Rosetta, Foldetta, polyPhen2_HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, Foldetta predicts a pathogenic outcome, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two pathogenic vs. two benign). Overall, the majority of predictions lean toward pathogenicity, and this does not contradict the ClinVar status, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.728858	Disordered	0.429104	Uncertain	0.296	0.949	0.750							-9.067	Likely Pathogenic	0.660	Likely Pathogenic	Likely Benign	0.440	Likely Benign	0.1295	0.3741		4.03	Destabilizing	2.3	3.36	Destabilizing	3.70	Destabilizing	0.29	Likely Benign	-0.84	Neutral	0.498	Possibly Damaging	0.119	Benign	4.10	Benign	0.00	Affected			-3	-2	-4.1	99.14
c.1895A>C	N632T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N632T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include Foldetta, premPS, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, PROVEAN, and FATHMM. The remaining tools—FoldX, Rosetta, and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic. Overall, the majority of predictions lean toward a benign impact, and this does not contradict any ClinVar annotation (none is available). Thus, based on the current computational evidence, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.042364	Structured	0.041437	Uncertain	0.938	0.254	0.000							-6.797	Likely Benign	0.371	Ambiguous	Likely Benign	0.541	Likely Pathogenic	0.1295	0.6809		1.14	Ambiguous	0.2	-0.58	Ambiguous	0.28	Likely Benign	0.39	Likely Benign	-4.48	Deleterious	0.214	Benign	0.062	Benign	-1.49	Pathogenic	0.13	Tolerated			0	0	2.8	-13.00
c.1162G>C	G388R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G388R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include premPS, PROVEAN, and AlphaMissense‑Optimized, whereas the remaining eleven tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default) uniformly predict a pathogenic impact. High‑accuracy methods further support pathogenicity: AlphaMissense‑Optimized indicates benign, but the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta outputs) both predict pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overall consensus of the majority of tools and the high‑accuracy predictions, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.736850	Disordered	0.420316	Uncertain	0.319	0.827	0.750							-9.142	Likely Pathogenic	0.694	Likely Pathogenic	Likely Benign	0.606	Likely Pathogenic	0.1296	0.4417		6.54	Destabilizing	8.5	4.79	Destabilizing	5.67	Destabilizing	0.31	Likely Benign	-0.74	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	1.32	Pathogenic	0.02	Affected			-3	-2	-4.1	99.14
c.1558T>A	S520T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S520T is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions come from premPS and PROVEAN, while pathogenic predictions are made by SGM‑Consensus, REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Four high‑accuracy methods were examined: AlphaMissense‑Optimized returned an uncertain result; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, was also uncertain. With three of the four high‑accuracy tools indicating pathogenicity and only two tools suggesting benign, the overall evidence points to a pathogenic effect. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.094817	Structured	0.084894	Uncertain	0.887	0.337	0.000							-8.432	Likely Pathogenic	0.822	Likely Pathogenic	Ambiguous	0.565	Likely Pathogenic	0.1296	0.5199		0.52	Ambiguous	0.0	0.52	Ambiguous	0.52	Ambiguous	0.34	Likely Benign	-2.41	Neutral	0.826	Possibly Damaging	0.872	Possibly Damaging	-1.28	Pathogenic	0.02	Affected			1	1	0.1	14.03
c.3005A>T	H1002L 2D AIThe SynGAP1 H1002L missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation and the absence of the variant in population databases, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.784345	Disordered	0.953758	Binding	0.285	0.900	0.500							-6.448	Likely Benign	0.556	Ambiguous	Likely Benign	0.157	Likely Benign	0.1296	0.5088											-3.12	Deleterious	0.801	Possibly Damaging	0.602	Possibly Damaging	2.79	Benign	0.13	Tolerated			-2	-3	7.0	-23.98
c.1253A>T	K418I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant K418I is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include REVEL, premPS, and FATHMM. In contrast, the majority of tools predict a pathogenic outcome: SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta provide uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, SGM‑Consensus as Likely Pathogenic, and Foldetta as Uncertain. Overall, the preponderance of evidence points to a pathogenic effect for K418I, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.104810	Structured	0.360134	Uncertain	0.948	0.263	0.000							-14.895	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.428	Likely Benign	0.1297	0.2432		0.51	Ambiguous	0.0	0.64	Ambiguous	0.58	Ambiguous	0.27	Likely Benign	-7.27	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.32	Benign	0.01	Affected			-2	-3	8.4	-15.01
c.1793T>G	L598R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L598R is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.007259	Structured	0.147872	Uncertain	0.953	0.154	0.000							-17.392	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.682	Likely Pathogenic	0.1297	0.0679		2.70	Destabilizing	0.5	3.06	Destabilizing	2.88	Destabilizing	2.23	Destabilizing	-5.87	Deleterious	0.999	Probably Damaging	0.973	Probably Damaging	3.10	Benign	0.00	Affected			-3	-2	-8.3	43.03
c.1907T>A	F636Y 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F636Y is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, SIFT, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, favors a pathogenic outcome (3/4 votes). High‑accuracy assessments further reveal AlphaMissense‑Optimized as benign, SGM Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as inconclusive. Stability‑based tools FoldX, Rosetta, and premPS are uncertain. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.041405	Structured	0.071525	Uncertain	0.913	0.264	0.000							-9.638	Likely Pathogenic	0.695	Likely Pathogenic	Likely Benign	0.394	Likely Benign	0.1297	0.1866		0.84	Ambiguous	0.1	0.51	Ambiguous	0.68	Ambiguous	0.90	Ambiguous	-2.89	Deleterious	0.927	Possibly Damaging	0.836	Possibly Damaging	3.40	Benign	0.08	Tolerated			7	3	-4.1	16.00
c.2987C>G	P996R 2D AIThe SynGAP1 missense variant P996R is listed in ClinVar (ID 2808854.0) as benign and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only SIFT predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the consensus of the majority of tools, including the high‑accuracy methods, indicates a benign impact. This prediction aligns with the ClinVar benign classification and does not contradict the existing clinical annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.775545	Disordered	0.942262	Binding	0.312	0.900	0.750	Benign		1				-4.457	Likely Benign	0.141	Likely Benign	Likely Benign	0.040	Likely Benign	0.1297	0.3385											-1.04	Neutral	0.144	Benign	0.085	Benign	4.26	Benign	0.01	Affected	4.32	4	-2	0	-2.9	59.07
c.3299G>T	G1100V 2D AIThe SynGAP1 missense variant G1100V is reported in gnomAD (variant ID 6‑33443851‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign); pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability result is available. Overall, the balance of evidence favors a benign classification for G1100V, and this conclusion does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.882776	Disordered	0.972009	Binding	0.360	0.865	0.875				6-33443851-G-T	1	6.51e-7	-2.362	Likely Benign	0.118	Likely Benign	Likely Benign	0.198	Likely Benign	0.1297	0.4036											-2.43	Neutral	0.992	Probably Damaging	0.906	Possibly Damaging	1.93	Pathogenic	0.01	Affected	3.77	5	-3	-1	4.6	42.08
c.176T>G	L59R 2D AISynGAP1 missense variant L59R is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome; Foldetta results are unavailable. The predictions are therefore split, with an equal number of benign and pathogenic calls, and the high‑accuracy tools provide contradictory signals. Consequently, the variant is most likely pathogenic based on the presence of multiple pathogenic predictions and the high‑accuracy AlphaMissense‑Optimized result, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.212910	Structured	0.484882	Uncertain	0.510	0.668	0.000							-4.037	Likely Benign	0.960	Likely Pathogenic	Likely Pathogenic	0.266	Likely Benign	0.1298	0.0600											-2.09	Neutral	0.943	Possibly Damaging	0.944	Probably Damaging	3.26	Benign	0.00	Affected			-3	-2	-8.3	43.03
c.2011G>A	D671N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant D671N is reported in gnomAD (6‑33441270‑G‑A) but has no ClinVar entry. Functional prediction tools that classify the variant as benign include REVEL, FoldX, Rosetta, Foldetta, premPS, FATHMM, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, while the SGM Consensus remains pathogenic. Overall, the predictions are split, with a slight bias toward benign outcomes from the majority of tools, but the consensus pathogenic signal from SGM and several high‑confidence predictors suggests uncertainty. The variant is most likely benign based on the preponderance of benign predictions, and this does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.194234	Structured	0.096749	Uncertain	0.677	0.370	0.000				6-33441270-G-A			-10.347	Likely Pathogenic	0.685	Likely Pathogenic	Likely Benign	0.184	Likely Benign	0.1298	0.6463		0.18	Likely Benign	0.1	0.39	Likely Benign	0.29	Likely Benign	0.19	Likely Benign	-3.19	Deleterious	0.887	Possibly Damaging	0.592	Possibly Damaging	3.36	Benign	0.02	Affected	3.39	27	1	2	0.0	-0.98
c.3239C>T	A1080V 2D AIThe SynGAP1 missense variant A1080V is listed in gnomAD (ID 6‑33443791‑C‑T) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; no Foldetta stability data are available. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.912647	Disordered	0.981457	Binding	0.303	0.900	0.750				6-33443791-C-T			-4.087	Likely Benign	0.229	Likely Benign	Likely Benign	0.124	Likely Benign	0.1298	0.6056											-1.06	Neutral	0.481	Possibly Damaging	0.144	Benign	3.99	Benign	0.04	Affected	3.77	5	0	0	2.4	28.05
c.1190G>A	C397Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C397Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are FoldX, Rosetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and the combined Foldetta method. Uncertain results come from AlphaMissense‑Default and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as pathogenic. Overall, the majority of tools and the high‑accuracy consensus lean toward a benign interpretation, and this does not contradict any ClinVar classification (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.429200	Structured	0.395774	Uncertain	0.778	0.551	0.250							-7.213	In-Between	0.397	Ambiguous	Likely Benign	0.455	Likely Benign	0.1299	0.5084		2.01	Destabilizing	2.3	8.64	Destabilizing	5.33	Destabilizing	0.12	Likely Benign	-1.82	Neutral	0.952	Possibly Damaging	0.497	Possibly Damaging	4.64	Benign	0.07	Tolerated			0	-2	-3.8	60.04
c.1225A>C	M409L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M409L is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; no tool predicts pathogenicity. The only inconclusive result is from premPS, which is marked uncertain and does not influence the overall benign consensus. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.150080	Structured	0.360643	Uncertain	0.884	0.219	0.000							-6.809	Likely Benign	0.286	Likely Benign	Likely Benign	0.199	Likely Benign	0.1299	0.4411		-0.04	Likely Benign	0.2	-0.08	Likely Benign	-0.06	Likely Benign	0.51	Ambiguous	-0.84	Neutral	0.206	Benign	0.324	Benign	4.21	Benign	0.57	Tolerated			4	2	1.9	-18.03
c.1225A>T	M409L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M409L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; no tool predicts pathogenicity. The only inconclusive result is premPS, which is listed as uncertain and does not influence the overall assessment. High‑accuracy methods confirm the benign prediction: AlphaMissense‑Optimized scores the variant as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) also classifies it as benign. Based on the collective evidence, the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.150080	Structured	0.360643	Uncertain	0.884	0.219	0.000							-6.809	Likely Benign	0.286	Likely Benign	Likely Benign	0.199	Likely Benign	0.1299	0.4411		-0.04	Likely Benign	0.2	-0.08	Likely Benign	-0.06	Likely Benign	0.51	Ambiguous	-0.84	Neutral	0.206	Benign	0.324	Benign	4.21	Benign	0.57	Tolerated			4	2	1.9	-18.03
c.1241T>A	M414K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M414K is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are limited to FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. FoldX and Foldetta provide uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta is unavailable. Based on the overwhelming agreement among the majority of prediction tools and the high‑accuracy methods, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.081712	Structured	0.329108	Uncertain	0.914	0.217	0.000							-13.537	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.503	Likely Pathogenic	0.1299	0.0888		1.18	Ambiguous	0.1	2.39	Destabilizing	1.79	Ambiguous	1.50	Destabilizing	-5.03	Deleterious	0.942	Possibly Damaging	0.860	Possibly Damaging	3.40	Benign	0.04	Affected			0	-1	-5.8	-3.02
c.2114A>C	K705T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant K705T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, Rosetta, Foldetta, premPS, and FATHMM, whereas pathogenic predictions are reported by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Uncertain calls are made by FoldX and AlphaMissense‑Optimized. High‑accuracy assessments indicate that the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, predicts a pathogenic effect, while Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign outcome. Overall, the balance of evidence leans toward a pathogenic interpretation, and this assessment does not conflict with ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.134866	Structured	0.379324	Uncertain	0.922	0.364	0.000							-8.617	Likely Pathogenic	0.826	Likely Pathogenic	Ambiguous	0.272	Likely Benign	0.1299	0.2612		0.60	Ambiguous	0.0	0.04	Likely Benign	0.32	Likely Benign	0.17	Likely Benign	-4.05	Deleterious	0.995	Probably Damaging	0.991	Probably Damaging	3.38	Benign	0.02	Affected			0	-1	3.2	-27.07
c.3002T>G	L1001R 2D AIThe SynGAP1 missense variant L1001R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.754692	Disordered	0.958507	Binding	0.269	0.902	0.375							-2.285	Likely Benign	0.320	Likely Benign	Likely Benign	0.091	Likely Benign	0.1299	0.0832											-1.09	Neutral	0.966	Probably Damaging	0.708	Possibly Damaging	2.67	Benign	0.00	Affected			-3	-2	-8.3	43.03
c.3067T>A	S1023T 2D AIThe SynGAP1 missense variant S1023T is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction, and Foldetta results are unavailable. Overall, the majority of high‑confidence tools predict a benign impact, and there is no conflict with ClinVar status. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.831250	Disordered	0.990262	Binding	0.322	0.750	0.500							-5.573	Likely Benign	0.360	Ambiguous	Likely Benign	0.092	Likely Benign	0.1299	0.5370											-1.62	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	2.49	Pathogenic	0.04	Affected			1	1	0.1	14.03
c.3344T>A	I1115N 2D AIThe SynGAP1 missense variant I1115N is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. No pathogenic predictions are present among the evaluated tools. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign based on current predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.889439	Disordered	0.892339	Binding	0.308	0.912	0.750							-4.018	Likely Benign	0.118	Likely Benign	Likely Benign	0.095	Likely Benign	0.1299	0.1270											-0.60	Neutral	0.009	Benign	0.011	Benign	2.77	Benign	0.08	Tolerated			-2	-3	-8.0	0.94
c.3371G>T	G1124V 2D AIThe SynGAP1 missense variant G1124V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools—polyPhen‑2 HumDiv and SIFT—suggest a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta results are unavailable, so they do not influence the assessment. Overall, the consensus of available predictions indicates that G1124V is most likely benign, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.837511	Disordered	0.833401	Binding	0.341	0.931	0.875							-6.980	Likely Benign	0.094	Likely Benign	Likely Benign	0.315	Likely Benign	0.1299	0.3888											-0.96	Neutral	0.586	Possibly Damaging	0.172	Benign	4.75	Benign	0.00	Affected			-1	-3	4.6	42.08
c.893C>G	P298R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P298R has no ClinVar entry and is not reported in gnomAD. Computational predictors fall into two consensus groups: benign predictions come from REVEL, FoldX, PROVEAN, SIFT, and AlphaMissense‑Optimized; pathogenic predictions come from SGM‑Consensus, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Uncertain results are reported only by Foldetta and premPS. High‑accuracy tools give a mixed picture: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta reports an uncertain stability change. Overall, the majority of evidence points toward a pathogenic effect, and this assessment is not contradicted by ClinVar, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.328603	Structured	0.268765	Uncertain	0.860	0.283	0.500							-11.427	Likely Pathogenic	0.733	Likely Pathogenic	Likely Benign	0.280	Likely Benign	0.1299	0.3872		0.45	Likely Benign	0.0	2.08	Destabilizing	1.27	Ambiguous	0.61	Ambiguous	-1.83	Neutral	0.997	Probably Damaging	0.952	Probably Damaging	2.03	Pathogenic	0.09	Tolerated			0	-2	-2.9	59.07
c.286G>C	G96R 2D AIThe SynGAP1 missense variant G96R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for G96R, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.657645	Disordered	0.599491	Binding	0.335	0.871	0.625							-3.872	Likely Benign	0.349	Ambiguous	Likely Benign	0.059	Likely Benign	0.1300	0.5031											-0.91	Neutral	0.687	Possibly Damaging	0.062	Benign	4.19	Benign	0.00	Affected			-3	-2	-4.1	99.14
c.3200C>G	P1067R 2D AIThe SynGAP1 missense variant P1067R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default is uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also predicts benign, while Foldetta’s stability analysis is unavailable. Taken together, the majority of reliable predictors and the high‑accuracy tools indicate a benign impact. This conclusion is not contradicted by ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.966441	Disordered	0.975099	Binding	0.459	0.907	0.875							-4.878	Likely Benign	0.376	Ambiguous	Likely Benign	0.167	Likely Benign	0.1300	0.3651											-2.74	Deleterious	0.971	Probably Damaging	0.580	Possibly Damaging	2.78	Benign	0.01	Affected			0	-2	-2.9	59.07
c.410T>G	L137R 2D AIThe SynGAP1 missense variant L137R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and FATHMM. All other evaluated tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—predict a pathogenic or likely pathogenic impact. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus is labeled Likely Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the collective predictions, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.553315	Disordered	0.639549	Binding	0.377	0.897	0.375							-11.595	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.334	Likely Benign	0.1300	0.0691											-3.50	Deleterious	0.998	Probably Damaging	0.994	Probably Damaging	3.60	Benign	0.00	Affected			-3	-2	-8.3	43.03
c.3796C>G	L1266V 2D AIThe SynGAP1 missense variant L1266V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: REVEL predicts a benign outcome, whereas all other evaluated algorithms (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.433034	Structured	0.802655	Binding	0.868	0.602	0.000							-10.024	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.125	Likely Benign	0.1301	0.3118											-2.53	Deleterious	0.995	Probably Damaging	0.890	Possibly Damaging	2.16	Pathogenic	0.00	Affected			2	1	0.4	-14.03
c.2269G>T	G757C 2D AIThe SynGAP1 missense variant G757C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.436924	Structured	0.830995	Binding	0.310	0.869	0.375							-6.652	Likely Benign	0.139	Likely Benign	Likely Benign	0.179	Likely Benign	0.1302	0.3630											-1.74	Neutral	0.997	Probably Damaging	0.870	Possibly Damaging	2.65	Benign	0.04	Affected			-3	-3	2.9	46.09
c.700C>T	R234W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 R234W missense variant is listed in ClinVar (ID 856396.0) with an “Uncertain” clinical significance and is present in gnomAD (variant ID 6‑33435551‑C‑T). Prediction tools that agree on a benign effect include premPS and FATHMM, whereas the majority of other in‑silico predictors (REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus) indicate a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain”; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is “Uncertain.” Overall, the preponderance of evidence points to a pathogenic effect, which is consistent with the ClinVar designation of uncertainty rather than a benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.239899	Structured	0.311558	Uncertain	0.804	0.322	0.000	Uncertain		1	6-33435551-C-T	3	1.86e-6	-12.625	Likely Pathogenic	0.947	Likely Pathogenic	Ambiguous	0.805	Likely Pathogenic	0.1302	0.4035		0.96	Ambiguous	0.3	0.69	Ambiguous	0.83	Ambiguous	0.13	Likely Benign	-5.52	Deleterious	0.997	Probably Damaging	0.803	Possibly Damaging	5.76	Benign	0.01	Affected	3.40	14	2	-3	3.6	30.03	262.8	39.6	-0.1	0.0	-0.2	0.2		X						Potentially Pathogenic	The guanidinium group of Arg234, located in a β-α loop between an anti-parallel β sheet strand (residues Gly227-Phe231) and an α helix (res. Ala236-Val250), forms a salt bridge with the carboxylate group of Glu238 in the α helix. Occasionally, it also bonds with the GAP domain residues Ser678 and Glu680. Thus, the positively charged Arg234 could contribute to the tertiary structure assembly between the PH and GAP domains. In contrast, the indole side chain of Trp234 in the variant is located on the protein surface in the variant simulations and is unable to form any interactions.
c.2146C>T	R716W 2D 3DClick to see structure in 3D Viewer AIClinVar has no entry for this SynGAP1 R716W variant, and it is present in the gnomAD database (ID 6‑33441611‑C‑T). Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, AlphaMissense‑Optimized, premPS, and Foldetta, while those that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic. With two high‑accuracy tools supporting benign and one supporting pathogenic, the overall prediction leans toward a benign effect. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.247041	Structured	0.419135	Uncertain	0.962	0.379	0.000				6-33441611-C-T	5	3.10e-6	-11.543	Likely Pathogenic	0.766	Likely Pathogenic	Likely Benign	0.339	Likely Benign	0.1303	0.3252		-0.11	Likely Benign	0.0	0.87	Ambiguous	0.38	Likely Benign	0.31	Likely Benign	-6.72	Deleterious	1.000	Probably Damaging	0.995	Probably Damaging	3.32	Benign	0.00	Affected	3.50	9	-3	2	3.6	30.03
c.2222C>G	P741R 2D AIThe SynGAP1 missense variant P741R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.885302	Disordered	0.493550	Uncertain	0.354	0.859	0.875							-4.434	Likely Benign	0.131	Likely Benign	Likely Benign	0.070	Likely Benign	0.1303	0.2712											-1.19	Neutral	0.642	Possibly Damaging	0.393	Benign	2.85	Benign	0.02	Affected			0	-2	-2.9	59.07
c.2564T>G	L855R 2D AIThe SynGAP1 missense variant L855R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.485558	Uncertain	0.285	0.823	0.625							-3.703	Likely Benign	0.229	Likely Benign	Likely Benign	0.086	Likely Benign	0.1303	0.1187											-1.62	Neutral	0.026	Benign	0.015	Benign	4.00	Benign	0.03	Affected			-3	-2	-8.3	43.03
c.1058T>G	L353R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L353R is not reported in ClinVar and is absent from gnomAD. In silico predictors largely agree on a deleterious effect: benign predictions are limited to REVEL, whereas the remaining tools—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all classify the variant as pathogenic. High‑accuracy assessments further support this view: AlphaMissense‑Optimized is uncertain, SGM‑Consensus predicts likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction contradicts the ClinVar status, which is currently unreported. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.137348	Structured	0.373584	Uncertain	0.926	0.315	0.000							-11.213	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	0.444	Likely Benign	0.1304	0.1145		3.60	Destabilizing	0.5	2.48	Destabilizing	3.04	Destabilizing	1.91	Destabilizing	-4.15	Deleterious	0.947	Possibly Damaging	0.454	Possibly Damaging	1.33	Pathogenic	0.01	Affected			-3	-2	-8.3	43.03
c.1758C>A	D586E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D586E missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Optimized, and Foldetta. Those that predict a pathogenic outcome are polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default; Rosetta is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split. Overall, the majority of evidence points to a benign effect. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.060549	Structured	0.066018	Uncertain	0.866	0.241	0.000							-3.233	Likely Benign	0.683	Likely Pathogenic	Likely Benign	0.367	Likely Benign	0.1304	0.5126		-0.42	Likely Benign	0.1	0.88	Ambiguous	0.23	Likely Benign	0.38	Likely Benign	-0.12	Neutral	0.929	Possibly Damaging	0.969	Probably Damaging	-1.20	Pathogenic	1.00	Tolerated			3	2	0.0	14.03
c.1758C>G	D586E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D586E missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default; Rosetta is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, the majority of evidence points to a benign impact. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.060549	Structured	0.066018	Uncertain	0.866	0.241	0.000							-3.233	Likely Benign	0.683	Likely Pathogenic	Likely Benign	0.367	Likely Benign	0.1304	0.5126		-0.42	Likely Benign	0.1	0.88	Ambiguous	0.23	Likely Benign	0.38	Likely Benign	-0.12	Neutral	0.929	Possibly Damaging	0.969	Probably Damaging	-1.20	Pathogenic	1.00	Tolerated			3	2	0.0	14.03
c.3323G>C	S1108T 2D AIThe SynGAP1 missense variant S1108T is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are not available. Overall, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.852992	Disordered	0.949221	Binding	0.324	0.886	0.875							-5.710	Likely Benign	0.105	Likely Benign	Likely Benign	0.078	Likely Benign	0.1304	0.5365											-1.49	Neutral	0.393	Benign	0.239	Benign	2.56	Benign	0.25	Tolerated			1	1	0.1	14.03
c.2600G>A	G867E 2D AIThe SynGAP1 missense variant G867E is catalogued in gnomAD (6‑33443152‑G‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Pathogenic predictions are reported by polyPhen‑2 HumDiv and polyPhen‑2 HumVar, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign effect, and this conclusion does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.517562	Disordered	0.657954	Binding	0.285	0.801	0.250				6-33443152-G-A	3	1.86e-6	-5.204	Likely Benign	0.492	Ambiguous	Likely Benign	0.105	Likely Benign	0.1305	0.3880											-1.57	Neutral	0.994	Probably Damaging	0.943	Probably Damaging	2.74	Benign	0.07	Tolerated	3.82	4	-2	0	-3.1	72.06
c.2809G>T	D937Y 2D AIThe SynGAP1 missense variant D937Y is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic versus four benign) lean toward a pathogenic impact. Thus, the variant is most likely pathogenic based on current computational evidence, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.819762	Disordered	0.963385	Binding	0.348	0.883	0.625							-4.720	Likely Benign	0.711	Likely Pathogenic	Likely Benign	0.137	Likely Benign	0.1305	0.7494											-2.52	Deleterious	1.000	Probably Damaging	0.983	Probably Damaging	2.67	Benign	0.05	Affected			-4	-3	2.2	48.09
c.3902C>A	P1301H 2D AIThe SynGAP1 missense variant P1301H is listed in ClinVar (ID 212356.0) with an “Uncertain” clinical significance and is present in gnomAD (variant ID 6‑33451776‑C‑A). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The high‑accuracy consensus methods report a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates “Likely Benign.” No Foldetta stability result is available. Overall, the majority of predictions, including the high‑accuracy consensus, support a benign classification, which does not contradict the ClinVar status of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.885064	Binding	0.447	0.841	0.875	Conflicting		2	6-33451776-C-A	5	3.10e-6	-5.756	Likely Benign	0.104	Likely Benign	Likely Benign	0.232	Likely Benign	0.1305	0.2965											-1.13	Neutral	0.642	Possibly Damaging	0.378	Benign	2.79	Benign	0.04	Affected	3.77	5	0	-2	-1.6	40.02
c.1109G>T	G370V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G370V is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster into two groups: benign (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score of Likely Benign) and pathogenic (FoldX, Rosetta, Foldetta, and FATHMM). High‑accuracy assessments further refine this picture: AlphaMissense‑Optimized predicts a benign effect, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign, whereas Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, reports a pathogenic outcome. Overall, the majority of evidence points toward a benign impact, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.461924	Structured	0.434325	Uncertain	0.359	0.720	0.500							-5.328	Likely Benign	0.094	Likely Benign	Likely Benign	0.427	Likely Benign	0.1306	0.4198		4.98	Destabilizing	3.8	5.61	Destabilizing	5.30	Destabilizing	-0.43	Likely Benign	0.03	Neutral	0.000	Benign	0.000	Benign	1.32	Pathogenic	0.29	Tolerated			-1	-3	4.6	42.08
c.1466T>G	L489R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L489R is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity are unanimous: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. No tool in the dataset predicts a benign effect. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized indicates pathogenicity; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a destabilizing, pathogenic effect. Based on the collective evidence, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which simply lacks an entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.191378	Structured	0.326126	Uncertain	0.949	0.234	0.125							-15.365	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.949	Likely Pathogenic	0.1306	0.1145		4.32	Destabilizing	0.3	4.90	Destabilizing	4.61	Destabilizing	1.74	Destabilizing	-5.86	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.61	Pathogenic	0.00	Affected			-3	-2	-8.3	43.03
c.1873C>G	L625V 2D AISynGAP1 missense variant L625V is listed in ClinVar with an uncertain significance (ClinVar ID 3392716.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and FATHMM, while pathogenic predictions are made by premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. Four tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) give inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points toward a pathogenic effect, which does not contradict the ClinVar uncertain status but suggests a higher likelihood of pathogenicity. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.229226	Structured	0.045896	Uncertain	0.966	0.215	0.000	Uncertain		1				-11.319	Likely Pathogenic	0.833	Likely Pathogenic	Ambiguous	0.480	Likely Benign	0.1306	0.3427		1.80	Ambiguous	0.7	1.69	Ambiguous	1.75	Ambiguous	1.42	Destabilizing	-2.96	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	3.07	Benign	0.01	Affected			2	1	0.4	-14.03
c.2036T>A	F679Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F679Y is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. Two tools give uncertain results: premPS and AlphaMissense‑Default. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) resolves to benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts benign. Overall, the majority of evidence indicates that F679Y is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.222385	Structured	0.129316	Uncertain	0.700	0.320	0.000							-5.842	Likely Benign	0.462	Ambiguous	Likely Benign	0.315	Likely Benign	0.1306	0.1954		0.48	Likely Benign	0.2	0.13	Likely Benign	0.31	Likely Benign	0.71	Ambiguous	-2.71	Deleterious	0.993	Probably Damaging	0.952	Probably Damaging	3.47	Benign	0.14	Tolerated			7	3	-4.1	16.00
c.2660C>G	P887R 2D AIThe SynGAP1 missense variant P887R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports Likely Benign. No Foldetta stability data are available, so it does not influence the assessment. Overall, the preponderance of evidence supports a benign classification for P887R, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.716283	Disordered	0.602269	Binding	0.348	0.925	0.500							-4.759	Likely Benign	0.201	Likely Benign	Likely Benign	0.091	Likely Benign	0.1306	0.2238											-1.06	Neutral	0.802	Possibly Damaging	0.413	Benign	2.76	Benign	1.00	Tolerated			0	-2	-2.9	59.07
c.2762T>G	L921R 2D AIThe SynGAP1 missense variant L921R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts benign, and Foldetta results are unavailable. Overall, the majority of high‑confidence tools predict a benign impact, and there is no conflict with ClinVar status. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.608892	Disordered	0.943282	Binding	0.311	0.845	0.375							-2.205	Likely Benign	0.563	Ambiguous	Likely Benign	0.217	Likely Benign	0.1306	0.0761											-1.19	Neutral	0.994	Probably Damaging	0.912	Probably Damaging	2.41	Pathogenic	0.00	Affected			-3	-2	-8.3	43.03
c.2912C>G	P971R 2D AIThe SynGAP1 missense variant P971R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.950334	Disordered	0.951523	Binding	0.545	0.905	0.625							-4.407	Likely Benign	0.149	Likely Benign	Likely Benign	0.042	Likely Benign	0.1306	0.3818											-1.01	Neutral	0.453	Possibly Damaging	0.078	Benign	3.91	Benign	0.00	Affected			0	-2	-2.9	59.07
c.3860C>A	P1287H 2D AIThe SynGAP1 missense variant P1287H is recorded in gnomAD (6‑33447908‑C‑A) and has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, SGM‑Consensus is likely benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) is not available for this variant. Based on the aggregate predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.827927	Disordered	0.813701	Binding	0.538	0.777	0.750				6-33447908-C-A			-3.606	Likely Benign	0.135	Likely Benign	Likely Benign	0.043	Likely Benign	0.1306	0.3448											-1.36	Neutral	0.938	Possibly Damaging	0.596	Possibly Damaging	2.80	Benign	0.00	Affected	3.77	5	-2	0	-1.6	40.02
c.493A>T	S165C 2D AIThe SynGAP1 missense variant S165C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also resolves to benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact for S165C, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.429200	Structured	0.509123	Binding	0.324	0.644	0.250							-8.425	Likely Pathogenic	0.367	Ambiguous	Likely Benign	0.304	Likely Benign	0.1306	0.5534											-1.92	Neutral	0.938	Possibly Damaging	0.498	Possibly Damaging	3.94	Benign	0.00	Affected			0	-1	3.3	16.06
c.1301T>A	V434D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V434D is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign are SIFT and FATHMM; all other evaluated algorithms—including REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), AlphaMissense‑Default, and ESM1b—predict it to be pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized returns a pathogenic score; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts pathogenicity. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming agreement among pathogenic predictors and the corroborating high‑accuracy tools, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.158265	Structured	0.342846	Uncertain	0.954	0.306	0.000							-14.765	Likely Pathogenic	0.983	Likely Pathogenic	Likely Pathogenic	0.592	Likely Pathogenic	0.1307	0.0741		3.26	Destabilizing	0.0	3.33	Destabilizing	3.30	Destabilizing	1.78	Destabilizing	-5.18	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.38	Benign	0.13	Tolerated			-2	-3	-7.7	15.96
c.1411T>A	S471T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S471T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only FATHMM predicts pathogenic. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign.” High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign; the SGM‑Consensus (3 benign vs. 1 pathogenic) is benign; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is benign. No prediction or stability result is inconclusive. Overall, the evidence overwhelmingly supports a benign classification, and this is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.305330	Structured	0.355411	Uncertain	0.888	0.261	0.000							-5.780	Likely Benign	0.072	Likely Benign	Likely Benign	0.257	Likely Benign	0.1307	0.5046		0.59	Ambiguous	0.2	-0.47	Likely Benign	0.06	Likely Benign	0.20	Likely Benign	-1.96	Neutral	0.000	Benign	0.000	Benign	-1.18	Pathogenic	0.09	Tolerated			1	1	0.1	14.03
c.1531G>A	G511R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G511R is listed in ClinVar as Pathogenic (ClinVar ID 1774641.0) and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, SIFT, and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts Pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates Pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive. Stability calculations from FoldX and Rosetta are uncertain, and premPS is unavailable. Overall, the majority of evidence points to a pathogenic impact, aligning with the ClinVar classification and not contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.244404	Uncertain	0.924	0.287	0.000	Likely Pathogenic		1				-11.327	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.416	Likely Benign	0.1307	0.4104		1.94	Ambiguous	0.3	1.32	Ambiguous	1.63	Ambiguous	0.94	Ambiguous	-7.72	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.26	Benign	0.06	Tolerated	3.37	35	-3	-2	-4.1	99.14	279.4	-159.9	0.0	0.0	0.7	0.1			X				X	Potentially Pathogenic	Gly511 is located in an α-helix (res. Gly502-Tyr518), facing hydrophobic residues in an inter-helix space (e.g., Leu610, Ile514) in the WT simulations. In contrast, in the variant simulations, the bulkier and positively charged guanidinium side chain of Arg511 forms a salt bridge with the carboxylate group of Glu217 or hydrogen bonds with the backbone carbonyl group of Leu610. Although the residue swap introduces a third positively charged residue in close vicinity (Arg511, Lys507, Arg515), the protein structure seems to remain stable in the variant simulations. Importantly, according to ClinVar, the residue swap alters the last nucleotide of an exon and is predicted to destroy the splice donor site, resulting in aberrant splicing and pathogenic status.	10.1016/j.ajhg.2020.11.011
c.1531G>C	G511R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G511R is listed in ClinVar (ID 452818.0) as Pathogenic and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic, the SGM‑Consensus as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Uncertain, which is treated as unavailable evidence. Overall, the majority of available predictions support a pathogenic impact, aligning with the ClinVar classification. Thus, the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.244404	Uncertain	0.924	0.287	0.000	Pathogenic		1				-11.327	Likely Pathogenic	0.991	Likely Pathogenic	Likely Pathogenic	0.415	Likely Benign	0.1307	0.4104		1.94	Ambiguous	0.3	1.32	Ambiguous	1.63	Ambiguous	0.94	Ambiguous	-7.72	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.26	Benign	0.06	Tolerated	3.37	35	-3	-2	-4.1	99.14	279.4	-159.9	0.0	0.0	0.7	0.1			X				X	Potentially Pathogenic	Gly511 is located in an α-helix (res. Gly502-Tyr518), facing hydrophobic residues in an inter-helix space (e.g., Leu610, Ile514) in the WT simulations. In contrast, in the variant simulations, the bulkier and positively charged guanidinium side chain of Arg511 forms a salt bridge with the carboxylate group of Glu217 or hydrogen bonds with the backbone carbonyl group of Leu610. Although the residue swap introduces a third positively charged residue in close vicinity (Arg511, Lys507, Arg515), the protein structure seems to remain stable in the variant simulations. Importantly, according to ClinVar, the residue swap alters the last nucleotide of an exon and is predicted to destroy the splice donor site, resulting in aberrant splicing and pathogenic status.	10.1016/j.ajhg.2020.11.011
c.1756G>C	D586H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D586H missense variant is not reported in ClinVar and has no gnomAD entry. Prediction tools cluster into two groups: benign predictions come from premPS and SIFT, while the remaining nine tools (SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) all indicate pathogenicity. The high‑accuracy methods reinforce this trend: AlphaMissense‑Optimized scores the variant as pathogenic, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also predicts pathogenicity. Foldetta, which integrates FoldX‑MD and Rosetta outputs, yields an uncertain result. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is consistent with the absence of ClinVar annotation, as there is no conflicting status to contradict the prediction. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.066018	Uncertain	0.866	0.241	0.000							-10.104	Likely Pathogenic	0.974	Likely Pathogenic	Likely Pathogenic	0.672	Likely Pathogenic	0.1307	0.5558		1.00	Ambiguous	0.3	0.89	Ambiguous	0.95	Ambiguous	0.26	Likely Benign	-3.44	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	-1.23	Pathogenic	0.17	Tolerated			1	-1	0.3	22.05
c.1943T>A	F648Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F648Y is not reported in ClinVar (ClinVar status: not listed) but is present in gnomAD (gnomAD ID: 6‑33441202‑T‑A). Prediction tools that agree on a benign effect include REVEL, SIFT, and FATHMM, whereas a majority of tools predict a pathogenic impact: premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and ESM1b. Predictions that are inconclusive or unavailable are FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the balance of evidence favors a pathogenic classification for F648Y. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.051831	Structured	0.346782	Uncertain	0.943	0.339	0.000				6-33441202-T-A	4	2.48e-6	-8.632	Likely Pathogenic	0.889	Likely Pathogenic	Ambiguous	0.407	Likely Benign	0.1307	0.1396		0.74	Ambiguous	0.1	0.94	Ambiguous	0.84	Ambiguous	1.11	Destabilizing	-2.99	Deleterious	0.984	Probably Damaging	0.913	Probably Damaging	3.41	Benign	0.11	Tolerated	3.37	30	3	7	-4.1	16.00
c.2086C>G	L696V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L696V variant is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that indicate a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas the majority of other in silico predictors (FoldX, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) report a pathogenic outcome; Rosetta remains inconclusive. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts benign, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. Overall, the preponderance of evidence points to a pathogenic effect for the variant, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.200174	Structured	0.390093	Uncertain	0.962	0.267	0.000	Uncertain		1				-11.909	Likely Pathogenic	0.745	Likely Pathogenic	Likely Benign	0.351	Likely Benign	0.1307	0.2830		2.35	Destabilizing	0.1	1.85	Ambiguous	2.10	Destabilizing	1.46	Destabilizing	-2.79	Deleterious	0.992	Probably Damaging	0.970	Probably Damaging	3.16	Benign	0.00	Affected	3.46	13	1	2	0.4	-14.03
c.2818G>T	G940C 2D AIThe SynGAP1 missense variant G940C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. There is no ClinVar entry to contradict this conclusion, so the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.889439	Disordered	0.920635	Binding	0.383	0.902	0.625							-8.158	Likely Pathogenic	0.097	Likely Benign	Likely Benign	0.089	Likely Benign	0.1307	0.4354											-0.40	Neutral	0.996	Probably Damaging	0.905	Possibly Damaging	2.70	Benign	0.11	Tolerated			-3	-3	2.9	46.09
c.2825C>G	P942R 2D AIThe SynGAP1 missense variant P942R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.878102	Binding	0.365	0.915	0.625							-5.405	Likely Benign	0.159	Likely Benign	Likely Benign	0.045	Likely Benign	0.1307	0.3693											-0.78	Neutral	0.411	Benign	0.139	Benign	2.36	Pathogenic	0.00	Affected			0	-2	-2.9	59.07
c.504T>A	H168Q 2D AIThe SynGAP1 missense variant H168Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of ClinVar or gnomAD entries—there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.433034	Structured	0.502450	Binding	0.402	0.678	0.125							-5.177	Likely Benign	0.189	Likely Benign	Likely Benign	0.093	Likely Benign	0.1307	0.3873											-0.85	Neutral	0.000	Benign	0.001	Benign	4.31	Benign	0.02	Affected			3	0	-0.3	-9.01
c.504T>G	H168Q 2D AIThe SynGAP1 missense variant H168Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of ClinVar or gnomAD entries—there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.433034	Structured	0.502450	Binding	0.402	0.678	0.125							-5.177	Likely Benign	0.189	Likely Benign	Likely Benign	0.090	Likely Benign	0.1307	0.3873											-0.85	Neutral	0.000	Benign	0.001	Benign	4.31	Benign	0.02	Affected			3	0	-0.3	-9.01
c.2255C>T	S752L 2D AIThe SynGAP1 missense variant S752L is listed in ClinVar with an “Uncertain” status (ClinVar ID 2143952.0) and is present in gnomAD (ID 6‑33441720‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact, which does not contradict the ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.604312	Disordered	0.690594	Binding	0.365	0.877	0.625	Uncertain		2	6-33441720-C-T	6	3.72e-6	-3.386	Likely Benign	0.182	Likely Benign	Likely Benign	0.195	Likely Benign	0.1308	0.5909											-2.09	Neutral	0.993	Probably Damaging	0.641	Possibly Damaging	1.51	Pathogenic	0.01	Affected	3.99	5	-3	-2	4.6	26.08
c.2275A>C	M759L 2D AIThe SynGAP1 missense variant M759L is listed in ClinVar with an uncertain significance (ClinVar ID 942432.0) and is present in gnomAD (gnomAD ID 6‑33441740‑A‑C). All evaluated in‑silico predictors agree on a benign effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign classifications. No tool predicts pathogenicity. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the computational evidence strongly supports a benign impact, which is consistent with the ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.879389	Binding	0.299	0.864	0.375	Uncertain		1	6-33441740-A-C	2	1.24e-6	-2.431	Likely Benign	0.093	Likely Benign	Likely Benign	0.048	Likely Benign	0.1308	0.4005											-0.53	Neutral	0.002	Benign	0.005	Benign	2.84	Benign	1.00	Tolerated	3.99	5	4	2	1.9	-18.03
c.2275A>T	M759L 2D AIThe SynGAP1 missense variant M759L is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. No pathogenic predictions are present among the evaluated tools. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.879389	Binding	0.299	0.864	0.375							-2.431	Likely Benign	0.093	Likely Benign	Likely Benign	0.048	Likely Benign	0.1308	0.4005											-0.53	Neutral	0.002	Benign	0.005	Benign	2.84	Benign	1.00	Tolerated	3.99	5	4	2	1.9	-18.03
c.953C>G	P318R 2D 3DClick to see structure in 3D Viewer AISynGAP1 P318R is not reported in ClinVar and is absent from gnomAD. In silico predictors that classify the variant as benign: none. Those that predict pathogenicity include SGM‑Consensus (Likely Pathogenic), REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Predictions from FoldX, Rosetta, and Foldetta are uncertain. High‑accuracy tools give a consistent pathogenic signal: AlphaMissense‑Optimized reports pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates likely pathogenic; Foldetta remains inconclusive. Overall, the consensus of the majority of predictors supports a pathogenic effect. This conclusion is not contradicted by ClinVar status, which is currently unclassified. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.111485	Structured	0.400936	Uncertain	0.858	0.234	0.000							-14.132	Likely Pathogenic	0.987	Likely Pathogenic	Likely Pathogenic	0.643	Likely Pathogenic	0.1308	0.3310		1.20	Ambiguous	0.1	0.70	Ambiguous	0.95	Ambiguous	1.01	Destabilizing	-8.01	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.84	Pathogenic	0.01	Affected			0	-2	-2.9	59.07
c.1159G>C	G387R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G387R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include premPS, PROVEAN, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. Tools that predict pathogenicity are SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign effect, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No predictions are missing or inconclusive. Overall, the majority of evidence (10 pathogenic vs. 4 benign) indicates the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.642678	Disordered	0.422910	Uncertain	0.293	0.861	0.750							-8.728	Likely Pathogenic	0.683	Likely Pathogenic	Likely Benign	0.516	Likely Pathogenic	0.1309	0.4356		4.13	Destabilizing	2.9	2.57	Destabilizing	3.35	Destabilizing	0.15	Likely Benign	-0.54	Neutral	0.003	Benign	0.004	Benign	1.32	Pathogenic	0.01	Affected			-3	-2	-4.1	99.14
c.2357T>A	L786H 2D AIThe SynGAP1 missense variant L786H is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score. Grouping by agreement, two tools predict benign, seven predict pathogenic, and AlphaMissense‑Optimized remains uncertain. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is inconclusive, but the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.882776	Disordered	0.655253	Binding	0.341	0.895	0.750							-5.892	Likely Benign	0.836	Likely Pathogenic	Ambiguous	0.168	Likely Benign	0.1309	0.1214											-3.72	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.79	Pathogenic	0.00	Affected			-2	-3	-7.0	23.98
c.107A>T	H36L 2D AIThe SynGAP1 missense variant H36L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely benign classification. AlphaMissense‑Optimized also reports benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the majority of evidence points to a benign effect. Thus, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.433974	Uncertain	0.334	0.834	0.375							-2.403	Likely Benign	0.129	Likely Benign	Likely Benign	0.095	Likely Benign	0.1310	0.6111											-1.73	Neutral	0.010	Benign	0.011	Benign	4.19	Benign	0.00	Affected			-2	-3	7.0	-23.98
c.1229G>A	S410N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S410N is predicted to be benign by all evaluated in‑silico tools. Consensus predictors (REVEL, SIFT, polyPhen‑2 HumDiv/HumVar, PROVEAN, premPS, FoldX, Rosetta, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly report a benign effect, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) classifies it as “Likely Benign.” High‑accuracy assessments likewise support a benign outcome: AlphaMissense‑Optimized is benign, the SGM‑Consensus is likely benign, and Foldetta (combining FoldX‑MD and Rosetta stability outputs) indicates a benign effect. ClinVar contains no entry for this variant, and it is not present in gnomAD. Based on the collective predictions, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.098513	Structured	0.349627	Uncertain	0.908	0.206	0.000							-2.901	Likely Benign	0.111	Likely Benign	Likely Benign	0.049	Likely Benign	0.1310	0.5471		-0.16	Likely Benign	0.1	-0.16	Likely Benign	-0.16	Likely Benign	0.38	Likely Benign	-0.91	Neutral	0.000	Benign	0.000	Benign	4.20	Benign	0.18	Tolerated			1	1	-2.7	27.03
c.2160C>A	D720E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D720E missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessments reinforce the benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign majority, and Foldetta also predicts benign stability. No prediction or folding result is missing or inconclusive. Overall, the variant is most likely benign based on the collective predictions, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.374039	Structured	0.450695	Uncertain	0.955	0.417	0.125							-5.527	Likely Benign	0.391	Ambiguous	Likely Benign	0.131	Likely Benign	0.1310	0.5275		-0.31	Likely Benign	0.1	-0.41	Likely Benign	-0.36	Likely Benign	0.23	Likely Benign	-2.46	Neutral	0.975	Probably Damaging	0.969	Probably Damaging	2.46	Pathogenic	0.15	Tolerated			3	2	0.0	14.03
c.2160C>G	D720E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D720E missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessments reinforce the benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign majority, and Foldetta also predicts benign stability. No prediction or folding result is missing or inconclusive. Overall, the variant is most likely benign based on the collective predictions, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.374039	Structured	0.450695	Uncertain	0.955	0.417	0.125							-5.527	Likely Benign	0.391	Ambiguous	Likely Benign	0.131	Likely Benign	0.1310	0.5275		-0.31	Likely Benign	0.1	-0.41	Likely Benign	-0.36	Likely Benign	0.23	Likely Benign	-2.46	Neutral	0.975	Probably Damaging	0.969	Probably Damaging	2.46	Pathogenic	0.15	Tolerated			3	2	0.0	14.03
c.2501T>G	M834R 2D AIThe SynGAP1 missense variant M834R is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and FATHMM. AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) leans toward benign (2 benign vs. 1 pathogenic votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence indicates a benign impact, and this conclusion does not contradict any ClinVar annotation, as none exists for M834R. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.585406	Disordered	0.640801	Binding	0.258	0.863	0.375							-2.621	Likely Benign	0.449	Ambiguous	Likely Benign	0.148	Likely Benign	0.1310	0.0837											-2.44	Neutral	0.812	Possibly Damaging	0.284	Benign	2.43	Pathogenic	0.00	Affected			0	-1	-6.4	24.99
c.1055C>A	T352N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T352N is listed in ClinVar as Benign (ClinVar ID 590151.0) and is present in the gnomAD database (gnomAD ID 6‑33437960‑C‑A). Across the broad panel of in‑silico predictors, 13 tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus) uniformly report a benign effect, whereas only FATHMM predicts pathogenicity. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is also benign. No predictions or stability analyses are missing or inconclusive. Overall, the computational evidence strongly supports a benign classification, consistent with the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.137348	Structured	0.367886	Uncertain	0.926	0.329	0.000	Likely Benign		1	6-33437960-C-A	2	1.24e-6	-4.817	Likely Benign	0.117	Likely Benign	Likely Benign	0.027	Likely Benign	0.1311	0.4358		0.20	Likely Benign	0.0	-0.04	Likely Benign	0.08	Likely Benign	0.45	Likely Benign	-0.92	Neutral	0.255	Benign	0.057	Benign	1.75	Pathogenic	0.19	Tolerated	3.37	25	0	0	-2.8	13.00	208.4	-14.5	-0.2	0.1	-0.1	0.0		X						Potentially Benign	Thr352 is located in a short α helical section within a loop connecting two β strands (res. Gly341-Pro349, res. Thr359-Pro364) originating from two different anti-parallel β sheets of the C2 domain. In the WT simulations, the side chain hydroxyl and backbone amide groups of Thr354 form hydrogen bonds with the backbone carbonyl group of Pro349 at the end of the preceding β strand. This arrangement likely stabilizes the α helical section and aids in folding, keeping the short secondary structure element intact in the variant simulations. However, the carboxamide group of the Asn352 side chain does not form hydrogen bonds with the backbone carbonyl group of Pro349. Instead, it packs against the cyclic ring and forms hydrogen bonds with the phenol group of the Tyr363 side chain in the other β strand.
c.2654C>G	P885R 2D AIThe SynGAP1 missense variant P885R is reported in gnomAD (ID 6‑33443206‑C‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. No Foldetta stability analysis is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign impact, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.690604	Disordered	0.636133	Binding	0.344	0.917	0.250				6-33443206-C-G	1	6.20e-7	-4.166	Likely Benign	0.308	Likely Benign	Likely Benign	0.072	Likely Benign	0.1311	0.3505											-1.99	Neutral	0.586	Possibly Damaging	0.377	Benign	2.84	Benign	0.00	Affected	4.32	4	-2	0	-2.9	59.07
c.3831C>A	H1277Q 2D AIThe SynGAP1 missense variant H1277Q is reported in gnomAD (ID 6‑33447879‑C‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 (HumDiv and HumVar), AlphaMissense‑Default, AlphaMissense‑Optimized, and ESM1b; pathogenic predictions come from PROVEAN, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic) and Foldetta data are unavailable. Overall, the majority of evidence points toward a benign effect, and this conclusion does not conflict with the absence of a ClinVar classification. Thus, the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.775545	Disordered	0.805725	Binding	0.562	0.718	0.750				6-33447879-C-A			-3.323	Likely Benign	0.325	Likely Benign	Likely Benign	0.078	Likely Benign	0.1311	0.2351											-5.34	Deleterious	0.004	Benign	0.010	Benign	2.14	Pathogenic	0.00	Affected	3.77	5	0	3	-0.3	-9.01
c.3831C>G	H1277Q 2D AIThe SynGAP1 missense variant H1277Q is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, polyPhen‑2 (HumDiv and HumVar), AlphaMissense‑Default, AlphaMissense‑Optimized, and ESM1b; pathogenic predictions come from PROVEAN, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 benign vs. 2 pathogenic). Foldetta results are not available. Overall, the majority of evidence points toward a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign based on current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.775545	Disordered	0.805725	Binding	0.562	0.718	0.750							-3.323	Likely Benign	0.325	Likely Benign	Likely Benign	0.078	Likely Benign	0.1311	0.2351											-5.34	Deleterious	0.004	Benign	0.010	Benign	2.14	Pathogenic	0.00	Affected	3.77	5	0	3	-0.3	-9.01
c.2294G>C	S765T 2D AIThe SynGAP1 missense variant S765T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. The predictions do not contradict ClinVar status, as ClinVar contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.370445	Structured	0.922652	Binding	0.335	0.865	0.250							-4.233	Likely Benign	0.215	Likely Benign	Likely Benign	0.094	Likely Benign	0.1312	0.6673											-1.12	Neutral	0.963	Probably Damaging	0.950	Probably Damaging	4.13	Benign	0.37	Tolerated			1	1	0.1	14.03
c.2720G>A	S907N 2D AIThe SynGAP1 missense variant S907N is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the majority‑vote SGM‑Consensus also reports a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) predict a pathogenic impact. The AlphaMissense‑Default score is uncertain, and no Foldetta stability assessment is available. High‑accuracy evaluations further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely benign, with no Foldetta data to contradict this. Overall, the preponderance of evidence points to a benign effect, and this assessment does not conflict with any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.661854	Binding	0.336	0.920	0.250							-4.520	Likely Benign	0.430	Ambiguous	Likely Benign	0.140	Likely Benign	0.1312	0.4585											-0.26	Neutral	0.951	Possibly Damaging	0.803	Possibly Damaging	2.66	Benign	0.08	Tolerated			1	1	-2.7	27.03
c.3143G>T	G1048V 2D AIThe SynGAP1 missense variant G1048V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are REVEL, polyPhen‑2 HumDiv, and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. Thus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.977651	Disordered	0.923876	Binding	0.346	0.916	0.750							-6.108	Likely Benign	0.079	Likely Benign	Likely Benign	0.520	Likely Pathogenic	0.1312	0.3688											-0.59	Neutral	0.958	Probably Damaging	0.787	Possibly Damaging	2.54	Benign	0.11	Tolerated			-1	-3	4.6	42.08
c.3350G>T	G1117V 2D AIThe SynGAP1 missense variant G1117V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while ESM1b is uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.882776	Disordered	0.853192	Binding	0.323	0.914	0.750							-7.251	In-Between	0.083	Likely Benign	Likely Benign	0.284	Likely Benign	0.1312	0.3680											-1.32	Neutral	0.011	Benign	0.014	Benign	4.57	Benign	0.04	Affected			-1	-3	4.6	42.08
c.1171G>C	G391R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G391R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that classify the variant as benign include premPS, PROVEAN, and SIFT, whereas those that predict pathogenicity comprise REVEL, FoldX, Rosetta, Foldetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further show AlphaMissense‑Optimized labeling the variant as benign, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a destabilizing, pathogenic effect. Overall, the majority of predictions lean toward pathogenicity, and this conclusion does not conflict with the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.637480	Disordered	0.409509	Uncertain	0.279	0.741	0.750							-9.115	Likely Pathogenic	0.709	Likely Pathogenic	Likely Benign	0.628	Likely Pathogenic	0.1313	0.4124		2.80	Destabilizing	1.3	3.86	Destabilizing	3.33	Destabilizing	0.32	Likely Benign	-0.95	Neutral	0.999	Probably Damaging	0.960	Probably Damaging	1.32	Pathogenic	0.17	Tolerated			-3	-2	-4.1	99.14
c.3417G>C	Q1139H 2D AIThe SynGAP1 missense variant Q1139H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.908098	Disordered	0.721191	Binding	0.313	0.866	1.000							-3.962	Likely Benign	0.125	Likely Benign	Likely Benign	0.265	Likely Benign	0.1313	0.3801											-2.40	Neutral	0.002	Benign	0.007	Benign	5.41	Benign	0.00	Affected			3	0	0.3	9.01
c.3417G>T	Q1139H 2D AIThe SynGAP1 missense variant Q1139H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Based on the preponderance of benign predictions and the lack of contradictory evidence, the variant is most likely benign. This assessment does not conflict with ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.908098	Disordered	0.721191	Binding	0.313	0.866	1.000							-3.962	Likely Benign	0.125	Likely Benign	Likely Benign	0.265	Likely Benign	0.1313	0.3801											-2.40	Neutral	0.002	Benign	0.007	Benign	5.41	Benign	0.00	Affected			3	0	0.3	9.01
c.458C>A	T153N 2D AIThe SynGAP1 missense variant T153N is listed in ClinVar (ID 984906.0) with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign outcome. In contrast, polyPhen‑2 (HumDiv and HumVar) predict pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence supports a benign classification, and this is consistent with the ClinVar “Uncertain” designation rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.501700	Disordered	0.502105	Binding	0.297	0.818	0.625	Conflicting		3				-0.739	Likely Benign	0.226	Likely Benign	Likely Benign	0.161	Likely Benign	0.1313	0.3363											0.88	Neutral	0.888	Possibly Damaging	0.537	Possibly Damaging	4.23	Benign	0.81	Tolerated	3.61	5	0	0	-2.8	13.00
c.2771C>G	P924R 2D AIThe SynGAP1 missense variant P924R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls from REVEL and ESM1b, whereas the remaining seven tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized) predict pathogenicity. Grouping by consensus, the pathogenic group outweighs the benign group. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized scores the variant as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. Foldetta data are unavailable. Overall, the preponderance of evidence indicates that P924R is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.521092	Disordered	0.971858	Binding	0.293	0.846	0.250							-6.024	Likely Benign	0.965	Likely Pathogenic	Likely Pathogenic	0.420	Likely Benign	0.1314	0.2083											-6.20	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	0.66	Pathogenic	0.00	Affected			0	-2	-2.9	59.07
c.3352A>C	S1118R 2D AIThe SynGAP1 missense variant S1118R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that S1118R is most likely benign, and this conclusion is consistent with the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.828802	Binding	0.310	0.919	0.750							-2.670	Likely Benign	0.553	Ambiguous	Likely Benign	0.175	Likely Benign	0.1314	0.3431											-0.74	Neutral	0.034	Benign	0.023	Benign	5.17	Benign	0.05	Affected	4.32	2	-1	0	-3.7	69.11
c.3354C>A	S1118R 2D AIThe SynGAP1 missense variant S1118R (ClinVar ID 2656489.0) is listed as ClinVar status Uncertain and is not present in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only SIFT predicts a pathogenic effect, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this is consistent with the ClinVar Uncertain designation rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.828802	Binding	0.310	0.919	0.750	Uncertain		1				-2.670	Likely Benign	0.553	Ambiguous	Likely Benign	0.166	Likely Benign	0.1314	0.3431											-0.74	Neutral	0.034	Benign	0.023	Benign	5.17	Benign	0.05	Affected	4.32	2	-1	0	-3.7	69.11
c.3354C>G	S1118R 2D AIThe SynGAP1 missense variant S1118R is listed in gnomAD (ID 6‑33443906‑C‑G) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Based on the collective evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.876521	Disordered	0.828802	Binding	0.310	0.919	0.750				6-33443906-C-G			-2.670	Likely Benign	0.553	Ambiguous	Likely Benign	0.165	Likely Benign	0.1314	0.3431											-0.74	Neutral	0.034	Benign	0.023	Benign	5.17	Benign	0.05	Affected	4.32	2	-1	0	-3.7	69.11
c.3700C>G	L1234V 2D AIThe SynGAP1 missense variant L1234V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Two tools, AlphaMissense‑Default and ESM1b, return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) has no available result. Overall, the balance of evidence leans toward a benign classification, and this assessment does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.599170	Disordered	0.575096	Binding	0.844	0.527	0.125							-7.863	In-Between	0.402	Ambiguous	Likely Benign	0.090	Likely Benign	0.1314	0.2918											-1.80	Neutral	0.898	Possibly Damaging	0.602	Possibly Damaging	1.54	Pathogenic	0.50	Tolerated			2	1	0.4	-14.03
c.2180A>C	N727T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N727T is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that classify the variant as benign include REVEL, Rosetta, premPS, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. FoldX gives an uncertain result and is therefore treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta (combining FoldX‑MD and Rosetta outputs) as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑vs‑2 split. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.538167	Disordered	0.442107	Uncertain	0.843	0.542	0.625							-6.900	Likely Benign	0.335	Likely Benign	Likely Benign	0.125	Likely Benign	0.1315	0.7181		0.52	Ambiguous	0.1	-0.18	Likely Benign	0.17	Likely Benign	0.04	Likely Benign	-3.08	Deleterious	0.987	Probably Damaging	0.980	Probably Damaging	2.25	Pathogenic	0.74	Tolerated			0	0	2.8	-13.00
c.2867C>T	S956F 2D AIThe SynGAP1 missense variant S956F is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. The predictions do not contradict any ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.984871	Disordered	0.957345	Binding	0.364	0.917	0.750							-6.654	Likely Benign	0.226	Likely Benign	Likely Benign	0.101	Likely Benign	0.1315	0.4943											-1.04	Neutral	0.832	Possibly Damaging	0.398	Benign	1.93	Pathogenic	0.39	Tolerated			-3	-2	3.6	60.10
c.3437C>G	P1146R 2D AIThe SynGAP1 missense variant P1146R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a pathogenic effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. Tools that agree on a benign effect are ESM1b, FATHMM, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of available predictions (seven pathogenic versus three benign) indicate that the variant is most likely pathogenic. This conclusion is not contradicted by ClinVar status, as the variant has no existing ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.919029	Disordered	0.732173	Binding	0.415	0.837	1.000							-3.826	Likely Benign	0.729	Likely Pathogenic	Likely Benign	0.603	Likely Pathogenic	0.1315	0.3193											-4.81	Deleterious	0.996	Probably Damaging	0.967	Probably Damaging	5.50	Benign	0.00	Affected			0	-2	-2.9	59.07
c.3499G>A	D1167N 2D AIThe SynGAP1 missense variant D1167N is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evaluated predictors (five pathogenic vs. three benign) lean toward a pathogenic interpretation. This prediction does not contradict any ClinVar status, as the variant is not yet catalogued in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.599170	Disordered	0.783999	Binding	0.336	0.798	0.500							-3.671	Likely Benign	0.924	Likely Pathogenic	Ambiguous	0.180	Likely Benign	0.1315	0.7940											-1.72	Neutral	0.995	Probably Damaging	0.963	Probably Damaging	2.33	Pathogenic	0.01	Affected			2	1	0.0	-0.98
c.1126G>C	G376R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G376R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include Rosetta, premPS, PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are SGM‑Consensus, REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. Foldetta reports an uncertain outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of tools (8 pathogenic vs. 5 benign) and the consensus from high‑accuracy methods lean toward a pathogenic interpretation. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.680603	Disordered	0.428979	Uncertain	0.326	0.869	0.625							-8.500	Likely Pathogenic	0.658	Likely Pathogenic	Likely Benign	0.589	Likely Pathogenic	0.1316	0.4027		3.48	Destabilizing	1.3	-0.46	Likely Benign	1.51	Ambiguous	0.30	Likely Benign	-1.21	Neutral	1.000	Probably Damaging	0.999	Probably Damaging	1.32	Pathogenic	0.09	Tolerated			-3	-2	-4.1	99.14
c.2052C>A	D684E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D684E missense variant has no ClinVar entry and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM. In contrast, a majority of predictors (SGM‑Consensus, FoldX, Foldetta, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) indicate a pathogenic impact; predictions from Rosetta and premPS are inconclusive and are treated as unavailable. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the consensus of these tools, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.153798	Uncertain	0.870	0.282	0.000							-9.506	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.362	Likely Benign	0.1316	0.6187		2.88	Destabilizing	0.9	1.48	Ambiguous	2.18	Destabilizing	0.66	Ambiguous	-3.99	Deleterious	0.910	Possibly Damaging	0.210	Benign	3.37	Benign	0.01	Affected			3	2	0.0	14.03
c.2052C>G	D684E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D684E is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas the majority of algorithms predict a deleterious effect: FoldX, Foldetta, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). Two methods (Rosetta and premPS) returned uncertain results. High‑accuracy assessments further support a damaging impact: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is pathogenic. Overall, the computational evidence overwhelmingly indicates that D684E is pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.153798	Uncertain	0.870	0.282	0.000							-9.506	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.362	Likely Benign	0.1316	0.6187		2.88	Destabilizing	0.9	1.48	Ambiguous	2.18	Destabilizing	0.66	Ambiguous	-3.99	Deleterious	0.910	Possibly Damaging	0.210	Benign	3.37	Benign	0.01	Affected			3	2	0.0	14.03
c.2741A>T	D914V 2D AIThe SynGAP1 missense variant D914V is listed in ClinVar (ID 2582846.0) with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign.” High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote) as benign; Foldetta results are unavailable. Overall, the balance of evidence points to a benign effect, and this conclusion does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.699094	Disordered	0.785987	Binding	0.320	0.892	0.250	Uncertain		1				-4.260	Likely Benign	0.723	Likely Pathogenic	Likely Benign	0.187	Likely Benign	0.1316	0.7249											-2.24	Neutral	0.999	Probably Damaging	0.986	Probably Damaging	2.64	Benign	0.01	Affected	3.77	5	-3	-2	7.7	-15.96
c.338G>T	G113V 2D AIThe SynGAP1 missense variant G113V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.784345	Disordered	0.639486	Binding	0.350	0.870	0.750							-3.752	Likely Benign	0.188	Likely Benign	Likely Benign	0.124	Likely Benign	0.1316	0.4002											-1.77	Neutral	0.838	Possibly Damaging	0.145	Benign	4.18	Benign	0.05	Affected			-1	-3	4.6	42.08
c.398T>A	L133Q 2D AIThe SynGAP1 missense variant L133Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that indicate a benign effect include REVEL, polyPhen‑2 HumVar, and FATHMM, whereas those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable. Based on the preponderance of pathogenic predictions and the high‑accuracy consensus, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.422041	Structured	0.718429	Binding	0.320	0.896	0.250							-9.054	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	0.317	Likely Benign	0.1316	0.0879											-2.65	Deleterious	0.535	Possibly Damaging	0.259	Benign	3.53	Benign	0.01	Affected			-2	-2	-7.3	14.97
c.2771C>A	P924H 2D AIThe SynGAP1 missense variant P924H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious outcome: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic. The Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the preponderance of computational evidence indicates that P924H is most likely pathogenic, and this conclusion does not contradict any existing ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.521092	Disordered	0.971858	Binding	0.293	0.846	0.250							-6.236	Likely Benign	0.957	Likely Pathogenic	Likely Pathogenic	0.457	Likely Benign	0.1317	0.3281											-5.87	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	0.65	Pathogenic	0.00	Affected			0	-2	-1.6	40.02
c.3061C>G	Q1021E 2D AIThe SynGAP1 missense variant Q1021E is evaluated by multiple in silico tools. Benign predictions come from REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions are reported by polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The AlphaMissense‑Default tool gives an uncertain result. The consensus prediction from the SGM framework, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized scores the variant as benign, and the SGM Consensus also indicates a likely benign effect. No Foldetta stability analysis is available for this residue. ClinVar contains no entry for this variant, and it is absent from gnomAD, so there is no external evidence to contradict the computational assessment. Based on the collective predictions, the variant is most likely benign, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.899122	Disordered	0.979641	Binding	0.326	0.763	0.500							-4.852	Likely Benign	0.545	Ambiguous	Likely Benign	0.137	Likely Benign	0.1317	0.2069											-1.21	Neutral	0.963	Probably Damaging	0.973	Probably Damaging	2.65	Benign	0.03	Affected			2	2	0.0	0.98
c.917T>A	V306D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V306D is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. All available in‑silico predictors that were evaluated return a pathogenic or likely‑pathogenic assessment: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool in the dataset predicts a benign effect. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, is pathogenic. Based on the unanimous pathogenic predictions, the variant is most likely pathogenic, and this conclusion does not contradict the current ClinVar status of uncertainty. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.363090	Structured	0.315026	Uncertain	0.896	0.287	0.125	Uncertain		1				-18.289	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	0.530	Likely Pathogenic	0.1317	0.0768		4.40	Destabilizing	0.3	4.29	Destabilizing	4.35	Destabilizing	2.44	Destabilizing	-5.44	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.74	Pathogenic	0.00	Affected	3.38	19	-2	-3	-7.7	15.96	212.3	-18.3	-0.2	0.4	0.0	0.2	X		X				X	Potentially Pathogenic	The isopropyl group of Val396, located at the beginning of an anti-parallel β sheet strand (res. Thr305-Asn315), packs against multiple hydrophobic residues (e.g., Leu274, Trp308, Ala271) in the WT simulations. However, in the variant simulations, the negatively charged carboxylate group of the Asp306 side chain is not suitable for this hydrophobic niche. Consequently, the side chain moves out to interact with Ser300 in the β strand (res. Met289-Arg299) and the guanidinium group of Arg299 in the β hairpin loop.In the third simulation, the residue swap disrupts the C2 domain secondary structure and tertiary assembly to a large degree when the amino group of the Lys297 side chain rotates to form a salt bridge with Asp306. This drastic effect could potentially reflect the challenge presented by the residue swap during the C2 domain folding. Because the residue swap affects the C2 domain structure, the SynGAP-membrane association could also be impacted. However, this is beyond the scope of the solvent-only simulations to unravel.
c.1226T>A	M409K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M409K has no ClinVar record and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, Rosetta, SIFT, and FATHMM, while pathogenic calls arise from premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default. Uncertain results are reported by FoldX, Foldetta, and AlphaMissense‑Optimized. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized is inconclusive; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, predicts pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is also inconclusive. Overall, the majority of evidence points toward a pathogenic effect, and this conclusion does not conflict with the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.150080	Structured	0.360643	Uncertain	0.884	0.219	0.000							-13.618	Likely Pathogenic	0.927	Likely Pathogenic	Ambiguous	0.490	Likely Benign	0.1318	0.0656		0.93	Ambiguous	0.3	0.29	Likely Benign	0.61	Ambiguous	1.45	Destabilizing	-4.26	Deleterious	0.769	Possibly Damaging	0.750	Possibly Damaging	4.18	Benign	0.40	Tolerated			0	-1	-5.8	-3.02
c.1940G>T	G647V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G647V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that assess sequence conservation and structural impact uniformly classify the substitution as benign: SIFT, PolyPhen‑2 (HumDiv and HumVar), REVEL, premPS, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a tolerated change. No tool predicts pathogenicity; only FoldX and Rosetta report uncertain stability effects, which are treated as unavailable evidence. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign; the SGM Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is benign; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts a benign effect. Therefore, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.048328	Structured	0.325524	Uncertain	0.936	0.356	0.000							-4.713	Likely Benign	0.126	Likely Benign	Likely Benign	0.115	Likely Benign	0.1318	0.3946		0.85	Ambiguous	0.1	-0.59	Ambiguous	0.13	Likely Benign	-0.13	Likely Benign	-1.77	Neutral	0.178	Benign	0.073	Benign	3.52	Benign	0.12	Tolerated			-1	-3	4.6	42.08
c.2131C>G	L711V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L711V is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33441596‑C‑G). Prediction tools that indicate a benign effect include REVEL, FATHMM, and AlphaMissense‑Optimized. The majority of other in silico predictors—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—classify the change as pathogenic, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports it as likely pathogenic. High‑accuracy assessments further show AlphaMissense‑Optimized as benign, SGM‑Consensus as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the preponderance of evidence points to a pathogenic effect, which does not conflict with the ClinVar designation of uncertain significance. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.308712	Structured	0.377436	Uncertain	0.950	0.364	0.000	Uncertain		1	6-33441596-C-G	1	6.20e-7	-10.045	Likely Pathogenic	0.709	Likely Pathogenic	Likely Benign	0.170	Likely Benign	0.1318	0.3010		3.48	Destabilizing	0.1	2.22	Destabilizing	2.85	Destabilizing	1.40	Destabilizing	-2.59	Deleterious	0.992	Probably Damaging	0.970	Probably Damaging	3.34	Benign	0.00	Affected	3.50	9	1	2	0.4	-14.03
c.3746G>T	R1249M 2D AIThe SynGAP1 missense variant R1249M is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a deleterious effect: pathogenic predictions come from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (which is “Likely Pathogenic” based on a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Benign predictions are limited to REVEL and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains pathogenic. No Foldetta stability analysis is available for this variant. Overall, the preponderance of evidence from multiple in‑silico tools indicates that R1249M is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.745909	Disordered	0.366265	Uncertain	0.874	0.556	0.875							-8.520	Likely Pathogenic	0.643	Likely Pathogenic	Likely Benign	0.232	Likely Benign	0.1318	0.2173											-4.59	Deleterious	1.000	Probably Damaging	0.979	Probably Damaging	1.68	Pathogenic	0.00	Affected			0	-1	6.4	-24.99
c.1138G>A	G380R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 G380R missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include premPS, PROVEAN, FATHMM, and AlphaMissense‑Optimized, while those that agree on a pathogenic effect are REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Rosetta is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts a benign outcome, Foldetta predicts a pathogenic outcome, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split. Overall, the majority of evidence (10 pathogenic vs. 4 benign) points to a pathogenic impact. The variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar assertion exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.724957	Disordered	0.432982	Uncertain	0.316	0.939	0.750							-9.205	Likely Pathogenic	0.635	Likely Pathogenic	Likely Benign	0.640	Likely Pathogenic	0.1319	0.3956		5.94	Destabilizing	2.6	0.90	Ambiguous	3.42	Destabilizing	0.11	Likely Benign	-0.86	Neutral	0.940	Possibly Damaging	0.459	Possibly Damaging	2.53	Benign	0.01	Affected			-3	-2	-4.1	99.14
c.1138G>C	G380R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 G380R missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include premPS, PROVEAN, FATHMM, and AlphaMissense‑Optimized, while those that agree on a pathogenic effect are REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Rosetta is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, Foldetta predicts pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split. Overall, the majority of tools (10 pathogenic vs 4 benign) and the Foldetta result support a pathogenic classification. Thus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.724957	Disordered	0.432982	Uncertain	0.316	0.939	0.750							-9.205	Likely Pathogenic	0.635	Likely Pathogenic	Likely Benign	0.619	Likely Pathogenic	0.1319	0.3956		5.94	Destabilizing	2.6	0.90	Ambiguous	3.42	Destabilizing	0.11	Likely Benign	-0.86	Neutral	0.940	Possibly Damaging	0.459	Possibly Damaging	2.53	Benign	0.01	Affected			-3	-2	-4.1	99.14
c.1492A>C	M498L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M498L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Only FATHMM predicts a pathogenic outcome, while Rosetta, Foldetta, and premPS are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM‑Consensus as Likely Benign, and Foldetta as Uncertain. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation and gnomAD presence, so there is no contradiction with existing clinical databases. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.092881	Structured	0.399612	Uncertain	0.932	0.158	0.000							2.556	Likely Benign	0.072	Likely Benign	Likely Benign	0.271	Likely Benign	0.1319	0.3551		-0.23	Likely Benign	0.1	-0.89	Ambiguous	-0.56	Ambiguous	-0.53	Ambiguous	0.62	Neutral	0.000	Benign	0.000	Benign	-1.24	Pathogenic	0.92	Tolerated			4	2	1.9	-18.03
c.1492A>T	M498L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M498L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all predict benign or likely benign. Only FATHMM predicts a pathogenic outcome, while Rosetta, Foldetta, and premPS are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM‑Consensus as likely benign, and Foldetta as uncertain. Overall, the majority of evidence supports a benign classification, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.092881	Structured	0.399612	Uncertain	0.932	0.158	0.000							2.556	Likely Benign	0.072	Likely Benign	Likely Benign	0.271	Likely Benign	0.1319	0.3551		-0.23	Likely Benign	0.1	-0.89	Ambiguous	-0.56	Ambiguous	-0.53	Ambiguous	0.62	Neutral	0.000	Benign	0.000	Benign	-1.24	Pathogenic	0.92	Tolerated			4	2	1.9	-18.03
c.1796G>T	C599F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C599F is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that assess the variant’s effect largely agree on a deleterious outcome: REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify it as pathogenic or likely pathogenic. Only premPS predicts a benign effect. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized reports pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. No prediction or folding‑stability result is missing or inconclusive. Based on the overwhelming majority of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.009865	Structured	0.151725	Uncertain	0.960	0.151	0.000							-13.969	Likely Pathogenic	0.985	Likely Pathogenic	Likely Pathogenic	0.902	Likely Pathogenic	0.1319	0.3073		3.72	Destabilizing	1.3	2.70	Destabilizing	3.21	Destabilizing	-0.42	Likely Benign	-10.95	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	-1.47	Pathogenic	0.00	Affected			-4	-2	0.3	44.04
c.3257C>G	P1086R 2D AIThe SynGAP1 missense variant P1086R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM. Those that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (two pathogenic vs. two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, more tools (five) predict pathogenicity than benign (three), and the high‑accuracy consensus is inconclusive. Therefore, the variant is most likely pathogenic based on the current predictions, and this assessment does not contradict any ClinVar status because the variant is not yet reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.849326	Disordered	0.977190	Binding	0.393	0.885	1.000							-5.190	Likely Benign	0.848	Likely Pathogenic	Ambiguous	0.205	Likely Benign	0.1319	0.3551											-3.42	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.86	Benign	0.00	Affected			0	-2	-2.9	59.07
c.3907G>T	G1303C 2D AIThe SynGAP1 missense variant G1303C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.871313	Disordered	0.886612	Binding	0.429	0.854	0.875							-5.286	Likely Benign	0.257	Likely Benign	Likely Benign	0.377	Likely Benign	0.1319	0.3681											-2.49	Neutral	0.997	Probably Damaging	0.961	Probably Damaging	2.76	Benign	0.02	Affected			-3	-3	2.9	46.09
c.1355T>A	V452D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V452D is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools largely agree on a deleterious effect: benign predictions are limited to FATHMM, while all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy methods reinforce this consensus: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming agreement among both general and high‑accuracy predictors, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.335645	Structured	0.315167	Uncertain	0.970	0.229	0.000							-15.793	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.630	Likely Pathogenic	0.1320	0.0610		3.92	Destabilizing	0.1	3.37	Destabilizing	3.65	Destabilizing	2.52	Destabilizing	-6.92	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	3.16	Benign	0.00	Affected			-2	-3	-7.7	15.96
c.2179A>C	N727H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant N727H is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Two tools (premPS and ESM1b) return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of predictions (six benign vs. five pathogenic) lean toward a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.538167	Disordered	0.442107	Uncertain	0.843	0.542	0.625							-7.308	In-Between	0.224	Likely Benign	Likely Benign	0.171	Likely Benign	0.1320	0.7186		0.13	Likely Benign	0.0	-0.02	Likely Benign	0.06	Likely Benign	0.51	Ambiguous	-3.18	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	2.13	Pathogenic	0.03	Affected			2	1	0.3	23.04
c.1082A>G	Q361R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q361R has no ClinVar entry and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, SIFT, premPS, PROVEAN, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and Rosetta; pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign; the SGM‑Consensus itself is benign; and Foldetta, which integrates FoldX‑MD (Uncertain) and Rosetta (Benign), yields a benign prediction. Overall, the consensus of available computational evidence indicates that the variant is most likely benign, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.305330	Structured	0.427593	Uncertain	0.945	0.534	0.250							-6.898	Likely Benign	0.289	Likely Benign	Likely Benign	0.296	Likely Benign	0.1321	0.2955		-0.88	Ambiguous	0.0	-0.07	Likely Benign	-0.48	Likely Benign	-0.20	Likely Benign	-0.56	Neutral	0.987	Probably Damaging	0.953	Probably Damaging	1.71	Pathogenic	0.41	Tolerated			1	1	-1.0	28.06
c.1366C>A	Q456K 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q456K is not reported in ClinVar and has no gnomAD entry. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, and FATHMM, whereas those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default; premPS and AlphaMissense‑Optimized are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of tools (six pathogenic vs five benign) and the SGM‑Consensus result point toward a pathogenic interpretation, while Foldetta suggests stability‑preserving benignity. Thus, the variant is most likely pathogenic based on current predictions, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.170161	Structured	0.302348	Uncertain	0.939	0.164	0.000							-13.768	Likely Pathogenic	0.806	Likely Pathogenic	Ambiguous	0.391	Likely Benign	0.1321	0.2547		0.21	Likely Benign	0.1	0.23	Likely Benign	0.22	Likely Benign	0.78	Ambiguous	-3.75	Deleterious	0.969	Probably Damaging	0.875	Possibly Damaging	3.36	Benign	0.13	Tolerated			1	1	-0.4	0.04
c.2485G>C	E829Q 2D AIThe SynGAP1 missense variant E829Q is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of reliable tools predict a benign impact, and there is no ClinVar entry to contradict this assessment. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.562014	Disordered	0.626045	Binding	0.326	0.882	0.375							-4.985	Likely Benign	0.531	Ambiguous	Likely Benign	0.225	Likely Benign	0.1321	0.7248											-1.83	Neutral	0.994	Probably Damaging	0.946	Probably Damaging	2.26	Pathogenic	0.00	Affected			2	2	0.0	-0.98
c.2864C>A	S955Y 2D AIThe SynGAP1 missense variant S955Y is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) support a benign classification. There is no ClinVar entry to contradict this assessment, so the variant is most likely benign based on current computational evidence. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.984871	Disordered	0.945325	Binding	0.350	0.924	0.750							-6.212	Likely Benign	0.216	Likely Benign	Likely Benign	0.077	Likely Benign	0.1321	0.4932											-1.62	Neutral	0.977	Probably Damaging	0.721	Possibly Damaging	2.32	Pathogenic	0.00	Affected			-3	-2	-0.5	76.10
c.3157A>C	S1053R 2D AIThe SynGAP1 missense variant S1053R is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate benign, while the majority‑vote SGM‑Consensus also reports a likely benign outcome. In contrast, the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic impact. The AlphaMissense‑Default score is uncertain, and no Foldetta stability assessment is available. High‑accuracy analyses reinforce the benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely benign, with no contradictory Foldetta data. Overall, the preponderance of evidence points to a benign effect for S1053R, and this assessment does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.981594	Disordered	0.885608	Binding	0.399	0.944	0.875							-6.421	Likely Benign	0.359	Ambiguous	Likely Benign	0.225	Likely Benign	0.1321	0.3820											0.43	Neutral	0.969	Probably Damaging	0.581	Possibly Damaging	5.33	Benign	0.59	Tolerated	3.77	5	-1	0	-3.7	69.11
c.3159C>A	S1053R 2D AIThe SynGAP1 missense variant S1053R is reported in gnomAD (variant ID 6‑33443711‑C‑A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. Overall, the majority of high‑accuracy predictors and consensus analyses indicate a benign impact. Thus, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.981594	Disordered	0.885608	Binding	0.399	0.944	0.875				6-33443711-C-A	1	1.10e-6	-6.421	Likely Benign	0.359	Ambiguous	Likely Benign	0.303	Likely Benign	0.1321	0.3820											0.43	Neutral	0.969	Probably Damaging	0.581	Possibly Damaging	5.33	Benign	0.59	Tolerated	3.77	5	-1	0	-3.7	69.11
c.3159C>G	S1053R 2D AIThe SynGAP1 missense variant S1053R is reported in gnomAD (ID 6‑33443711‑C‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, and the high‑accuracy consensus methods give a benign verdict: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports “Likely Benign.” Foldetta, a protein‑folding stability predictor combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign impact. The predictions do not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.981594	Disordered	0.885608	Binding	0.399	0.944	0.875				6-33443711-C-G			-6.421	Likely Benign	0.359	Ambiguous	Likely Benign	0.304	Likely Benign	0.1321	0.3820											0.43	Neutral	0.969	Probably Damaging	0.581	Possibly Damaging	5.33	Benign	0.59	Tolerated	3.77	5	-1	0	-3.7	69.11
c.359G>T	G120V 2D AIThe SynGAP1 missense variant G120V is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is not contradicted by any ClinVar status (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.707965	Disordered	0.659993	Binding	0.359	0.887	0.750							-4.571	Likely Benign	0.107	Likely Benign	Likely Benign	0.036	Likely Benign	0.1321	0.3883											-0.68	Neutral	0.000	Benign	0.000	Benign	4.28	Benign	0.19	Tolerated			-1	-3	4.6	42.08
c.1591T>C	C531R 2D AIThe SynGAP1 missense variant C531R is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include FoldX, Rosetta, Foldetta, and polyPhen‑2 HumVar, whereas the remaining tools—REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict it to be pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar classification because the variant is currently unreported in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.281712	Structured	0.017941	Uncertain	0.878	0.401	0.000							-12.600	Likely Pathogenic	0.966	Likely Pathogenic	Likely Pathogenic	0.619	Likely Pathogenic	0.1322	0.1566		0.31	Likely Benign	2.0	-0.27	Likely Benign	0.02	Likely Benign	1.40	Destabilizing	-9.85	Deleterious	0.929	Possibly Damaging	0.385	Benign	-1.24	Pathogenic	0.00	Affected			-4	-3	-7.0	53.05
c.2942G>T	G981V 2D AIThe SynGAP1 missense variant G981V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact for G981V, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.798249	Disordered	0.970320	Binding	0.275	0.897	0.625							-3.873	Likely Benign	0.714	Likely Pathogenic	Likely Benign	0.156	Likely Benign	0.1322	0.3861											-2.10	Neutral	0.997	Probably Damaging	0.958	Probably Damaging	3.75	Benign	0.00	Affected			-1	-3	4.6	42.08
c.3151G>T	G1051C 2D AIThe SynGAP1 missense variant G1051C is listed in ClinVar as Pathogenic and is not reported in gnomAD. Functional prediction tools show a split assessment: benign calls come from REVEL, PROVEAN, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized, while pathogenic calls come from polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. High‑accuracy methods give a benign result from AlphaMissense‑Optimized; the SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is tied (2 benign vs. 2 pathogenic) and therefore inconclusive, and Foldetta’s stability prediction is unavailable. Overall, the majority of predictions lean toward a benign effect, which contradicts the ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.987317	Disordered	0.900141	Binding	0.358	0.936	0.875	Likely Pathogenic		1				-9.050	Likely Pathogenic	0.122	Likely Benign	Likely Benign	0.497	Likely Benign	0.1322	0.4612											-0.90	Neutral	0.971	Probably Damaging	0.750	Possibly Damaging	-0.74	Pathogenic	0.10	Tolerated	3.77	5	-3	-3	2.9	46.09
c.3263G>T	S1088I 2D AIThe SynGAP1 missense variant S1088I is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33443815‑G‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and FATHMM, while those that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. AlphaMissense‑Optimized is uncertain, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the balance of evidence, the variant is most likely benign; this assessment does not contradict ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.910643	Disordered	0.975261	Binding	0.336	0.889	1.000				6-33443815-G-T			-4.893	Likely Benign	0.891	Likely Pathogenic	Ambiguous	0.288	Likely Benign	0.1322	0.5712											-2.05	Neutral	0.997	Probably Damaging	0.995	Probably Damaging	2.62	Benign	0.01	Affected	3.77	5	-2	-1	5.3	26.08
c.683C>A	T228K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T228K is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Foldetta, and FATHMM, whereas the majority of tools predict a pathogenic impact: SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Two tools give uncertain results (Rosetta and premPS). High‑accuracy methods further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, while Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. Overall, the balance of evidence favors a pathogenic classification, and this conclusion does not contradict any existing ClinVar annotation because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.104810	Structured	0.321733	Uncertain	0.829	0.316	0.125							-9.143	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic	0.676	Likely Pathogenic	0.1322	0.3590		0.03	Likely Benign	0.1	0.87	Ambiguous	0.45	Likely Benign	0.70	Ambiguous	-3.00	Deleterious	0.906	Possibly Damaging	0.521	Possibly Damaging	5.60	Benign	0.02	Affected			0	-1	-3.2	27.07
c.1076C>G	T359R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant T359R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on benign effects include REVEL, Rosetta, Foldetta, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, ESM1b, and FATHMM. Uncertain results come from FoldX, premPS, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, more tools favor a benign outcome, but a significant minority predict pathogenicity, leaving the variant’s clinical significance unresolved. The variant is most likely benign based on the prevailing predictions, and this does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.281712	Structured	0.414952	Uncertain	0.939	0.480	0.250							-8.675	Likely Pathogenic	0.402	Ambiguous	Likely Benign	0.157	Likely Benign	0.1323	0.3748		-0.74	Ambiguous	0.1	-0.20	Likely Benign	-0.47	Likely Benign	0.54	Ambiguous	-2.86	Deleterious	0.627	Possibly Damaging	0.091	Benign	1.75	Pathogenic	0.23	Tolerated			-1	-1	-3.8	55.08
c.1114G>A	G372R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G372R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Optimized. Those that agree on a pathogenic effect are REVEL, Rosetta, Foldetta, SIFT, FATHMM, and AlphaMissense‑Default. Two tools, FoldX and ESM1b, returned uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicting pathogenic, and Foldetta predicting pathogenic. Overall, the majority of predictions (seven pathogenic vs. five benign) and the consensus of high‑accuracy methods indicate a pathogenic effect. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.433034	Structured	0.430335	Uncertain	0.322	0.774	0.375							-7.344	In-Between	0.617	Likely Pathogenic	Likely Benign	0.572	Likely Pathogenic	0.1323	0.4313		1.49	Ambiguous	0.3	2.87	Destabilizing	2.18	Destabilizing	0.20	Likely Benign	-0.61	Neutral	0.001	Benign	0.001	Benign	-0.74	Pathogenic	0.02	Affected			-3	-2	-4.1	99.14
c.1114G>C	G372R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G372R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, Rosetta, Foldetta, SIFT, FATHMM, and AlphaMissense‑Default. Two tools (FoldX and ESM1b) give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as pathogenic. Overall, the majority of predictions (seven pathogenic vs five benign) indicate that the variant is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.433034	Structured	0.430335	Uncertain	0.322	0.774	0.375							-7.344	In-Between	0.617	Likely Pathogenic	Likely Benign	0.572	Likely Pathogenic	0.1323	0.4313		1.49	Ambiguous	0.3	2.87	Destabilizing	2.18	Destabilizing	0.20	Likely Benign	-0.61	Neutral	0.001	Benign	0.001	Benign	-0.74	Pathogenic	0.02	Affected			-3	-2	-4.1	99.14
c.1240A>C	M414L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M414L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, PROVEAN, SIFT, and FATHMM, while polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default predict a pathogenic outcome. Uncertain predictions come from premPS and ESM1b. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign verdict; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts benign. Overall, the preponderance of evidence indicates that M414L is most likely benign, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.081712	Structured	0.329108	Uncertain	0.914	0.217	0.000							-7.980	In-Between	0.779	Likely Pathogenic	Likely Benign	0.336	Likely Benign	0.1323	0.4236		0.26	Likely Benign	0.0	0.33	Likely Benign	0.30	Likely Benign	0.64	Ambiguous	-2.40	Neutral	0.559	Possibly Damaging	0.495	Possibly Damaging	3.63	Benign	0.90	Tolerated			4	2	1.9	-18.03
c.1240A>T	M414L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M414L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, PROVEAN, SIFT, and FATHMM, while polyPhen‑2 (HumDiv and HumVar) and AlphaMissense‑Default predict a pathogenic outcome. Uncertain predictions come from premPS and ESM1b. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields a benign verdict; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts benign. Overall, the preponderance of evidence indicates that M414L is most likely benign, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.081712	Structured	0.329108	Uncertain	0.914	0.217	0.000							-7.980	In-Between	0.779	Likely Pathogenic	Likely Benign	0.336	Likely Benign	0.1323	0.4236		0.26	Likely Benign	0.0	0.33	Likely Benign	0.30	Likely Benign	0.64	Ambiguous	-2.40	Neutral	0.559	Possibly Damaging	0.495	Possibly Damaging	3.63	Benign	0.90	Tolerated			4	2	1.9	-18.03
c.269T>A	V90E 2D AIThe SynGAP1 missense variant V90E is listed in ClinVar (ID 971665.0) with an uncertain significance status and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all predict benign. Only two tools—SIFT and AlphaMissense‑Default—suggest a pathogenic outcome. When the high‑accuracy consensus is considered, AlphaMissense‑Optimized remains benign, and the SGM Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign effect. No Foldetta stability assessment is available for this variant. Overall, the preponderance of evidence points to a benign impact, which does not contradict the ClinVar uncertain classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.570702	Disordered	0.542047	Binding	0.343	0.873	0.500	Uncertain		1				-4.079	Likely Benign	0.703	Likely Pathogenic	Likely Benign	0.108	Likely Benign	0.1323	0.2233											-0.38	Neutral	0.001	Benign	0.000	Benign	4.00	Benign	0.00	Affected	4.32	1	-2	-2	-7.7	29.98
c.3211G>T	G1071C 2D AIThe SynGAP1 missense variant G1071C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; the Foldetta stability analysis is unavailable. Overall, the majority of evidence—including the consensus and high‑accuracy predictions—supports a benign classification, and this is consistent with the lack of ClinVar annotation. Thus, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.983740	Binding	0.313	0.905	0.875							-5.364	Likely Benign	0.305	Likely Benign	Likely Benign	0.182	Likely Benign	0.1323	0.4227											-2.16	Neutral	0.997	Probably Damaging	0.889	Possibly Damaging	4.01	Benign	0.00	Affected			-3	-3	2.9	46.09
c.2720G>C	S907T 2D AIThe SynGAP1 missense variant S907T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The only tools that predict a pathogenic outcome are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.661854	Binding	0.336	0.920	0.250							-4.794	Likely Benign	0.220	Likely Benign	Likely Benign	0.178	Likely Benign	0.1324	0.6352											-0.53	Neutral	0.992	Probably Damaging	0.846	Possibly Damaging	2.66	Benign	0.93	Tolerated			1	1	0.1	14.03
c.3020G>T	S1007I 2D AIThe SynGAP1 missense variant S1007I is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas a majority of tools (PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, AlphaMissense‑Default) predict a pathogenic impact. The remaining tools, ESM1b and AlphaMissense‑Optimized, return uncertain results. High‑accuracy assessments further support a deleterious interpretation: the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as pathogenic; AlphaMissense‑Optimized remains uncertain, and Foldetta data are unavailable. Overall, the preponderance of evidence from both conventional and high‑accuracy predictors indicates that the S1007I variant is most likely pathogenic, with no conflict with ClinVar status because the variant has not yet been reported there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.671169	Disordered	0.925648	Binding	0.295	0.899	0.750							-7.800	In-Between	0.920	Likely Pathogenic	Ambiguous	0.126	Likely Benign	0.1324	0.4769											-2.55	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.65	Benign	0.00	Affected			-1	-2	5.3	26.08
c.698G>A	C233Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C233Y is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect are Rosetta and FATHMM, whereas the remaining tools—SGM‑Consensus, REVEL, FoldX, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact; premPS is uncertain. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic (3 pathogenic vs. 1 benign); and Foldetta, which integrates FoldX‑MD and Rosetta outputs, is pathogenic. Thus, the variant is most likely pathogenic based on the aggregate predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.239899	Structured	0.306787	Uncertain	0.868	0.322	0.000							-17.893	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.904	Likely Pathogenic	0.1324	0.5284		13.15	Destabilizing	4.6	0.04	Likely Benign	6.60	Destabilizing	0.71	Ambiguous	-9.79	Deleterious	0.940	Possibly Damaging	0.459	Possibly Damaging	5.71	Benign	0.00	Affected	4.29	391	0	-2	-3.8	60.04	248.9	-63.0	0.0	0.3	0.0	0.4	X						X	Potentially Pathogenic	The introduced residue Tyr233 is located in a β-α loop between an anti-parallel β sheet strand (res. Gly227-Ala232) and an α helix (residues Ala236-Val250). Although the thiol group of a cysteine side chain is not a strong hydrogen bond acceptor or donor, it facilitates hydrogen bonding between Cys233 and the backbone carbonyl of Ala232 in the WT simulations. In the variant simulations, the bulky phenol ring of the Tyr233 side chain stacks with the indole ring of the Trp242 side chain. This interaction could alter the tertiary assembly of the β sheet and α helix due to the residue swap. Indeed, in the second replica simulation, the protein structure begins to unfold to accommodate the introduced Tyr233 side chain.	10.1016/j.ajhg.2020.11.011
c.3337G>T	G1113C 2D AIThe SynGAP1 missense variant G1113C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. ESM1b is uncertain, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.905695	Disordered	0.900456	Binding	0.327	0.910	0.875							-7.917	In-Between	0.128	Likely Benign	Likely Benign	0.130	Likely Benign	0.1325	0.4956											-1.64	Neutral	0.999	Probably Damaging	0.917	Probably Damaging	2.50	Benign	0.06	Tolerated			-3	-3	2.9	46.09
c.1436G>T	R479L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant R479L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions (REVEL, FoldX, Rosetta, premPS, SIFT, FATHMM) and pathogenic predictions (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default). AlphaMissense‑Optimized is uncertain. High‑accuracy assessments give mixed results: AlphaMissense‑Optimized remains uncertain; the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts benign. No single metric dominates, and the overall evidence is balanced. Therefore, the variant’s pathogenicity is inconclusive; it is not contradicted by ClinVar status, which has no entry for this change. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.216401	Structured	0.419256	Uncertain	0.820	0.249	0.000							-11.118	Likely Pathogenic	0.832	Likely Pathogenic	Ambiguous	0.265	Likely Benign	0.1326	0.3624		0.45	Likely Benign	0.1	0.12	Likely Benign	0.29	Likely Benign	0.39	Likely Benign	-4.21	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	3.38	Benign	0.15	Tolerated			-3	-2	8.3	-43.03
c.1759A>T	R587W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R587W is not reported in ClinVar and is present in gnomAD (ID 6‑33440811‑A‑T). Functional prediction tools show a split assessment: benign predictions come from FoldX, Rosetta, and Foldetta, whereas pathogenic predictions are reported by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: premPS and AlphaMissense‑Optimized. High‑accuracy consensus methods further clarify the picture: the SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, indicates a likely pathogenic effect, whereas Foldetta, a protein‑folding stability predictor combining FoldX‑MD and Rosetta outputs, classifies the variant as benign. AlphaMissense‑Optimized remains inconclusive. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion does not conflict with the ClinVar status, which currently lacks an entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.054297	Structured	0.077330	Uncertain	0.862	0.216	0.000				6-33440811-A-T	1	6.20e-7	-15.383	Likely Pathogenic	0.879	Likely Pathogenic	Ambiguous	0.692	Likely Pathogenic	0.1326	0.3992		-0.01	Likely Benign	0.1	-0.44	Likely Benign	-0.23	Likely Benign	0.76	Ambiguous	-7.17	Deleterious	1.000	Probably Damaging	0.985	Probably Damaging	-1.33	Pathogenic	0.01	Affected	3.37	35	-3	2	3.6	30.03
c.2249G>A	G750E 2D AISynGAP1 missense variant G750E is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.618285	Disordered	0.646832	Binding	0.348	0.866	0.625	Uncertain		1				-2.618	Likely Benign	0.413	Ambiguous	Likely Benign	0.146	Likely Benign	0.1326	0.3768											-2.27	Neutral	1.000	Probably Damaging	0.982	Probably Damaging	2.49	Pathogenic	0.01	Affected	3.99	5	0	-2	-3.1	72.06
c.280C>A	P94T 2D AIThe SynGAP1 missense variant P94T is reported in gnomAD (variant ID 6‑33425888‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign status. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Consequently, the collective evidence indicates that P94T is most likely benign, and this assessment does not contradict any ClinVar classification because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.671169	Disordered	0.570978	Binding	0.350	0.869	0.625				6-33425888-C-A	1	6.20e-7	-4.254	Likely Benign	0.085	Likely Benign	Likely Benign	0.088	Likely Benign	0.1326	0.4789											-2.35	Neutral	0.198	Benign	0.015	Benign	4.12	Benign	0.00	Affected	4.32	1	-1	0	0.9	3.99
c.3266G>T	G1089V 2D AIThe SynGAP1 missense variant G1089V is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenic. Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic impact for G1089V. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.891961	Disordered	0.976771	Binding	0.366	0.890	1.000							-4.809	Likely Benign	0.527	Ambiguous	Likely Benign	0.182	Likely Benign	0.1326	0.4413											-2.81	Deleterious	0.984	Probably Damaging	0.722	Possibly Damaging	2.40	Pathogenic	0.00	Affected			-1	-3	4.6	42.08
c.3376G>T	G1126C 2D AIThe SynGAP1 missense variant G1126C is listed in ClinVar (ID 469157.0) with an “Uncertain” status and is present in gnomAD (6‑33443928‑G‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Tools that predict a pathogenic effect are SIFT and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is consistent with the ClinVar “Uncertain” classification rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.894241	Disordered	0.837209	Binding	0.345	0.918	0.875	Uncertain		1	6-33443928-G-T	11	7.35e-6	-9.389	Likely Pathogenic	0.113	Likely Benign	Likely Benign	0.449	Likely Benign	0.1326	0.4427											-1.40	Neutral	0.005	Benign	0.005	Benign	4.74	Benign	0.02	Affected	3.77	5	-3	-3	2.9	46.09
c.1868T>G	L623R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L623R is not reported in ClinVar (ClinVar status: not listed) and is absent from gnomAD (gnomAD ID: none). Prediction tools that assess pathogenicity unanimously classify the variant as deleterious: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a benign effect. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. All available evidence points to a pathogenic impact. Thus, the variant is most likely pathogenic, with no contradiction to ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.175930	Structured	0.060667	Uncertain	0.962	0.211	0.000							-13.718	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.795	Likely Pathogenic	0.1327	0.0615		4.08	Destabilizing	1.4	3.28	Destabilizing	3.68	Destabilizing	2.31	Destabilizing	-5.98	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.55	Pathogenic	0.00	Affected			-3	-2	-8.3	43.03
c.1910C>G	S637C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S637C is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that classify the variant as benign include REVEL, FoldX, Foldetta, premPS, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. High‑accuracy methods give the following results: AlphaMissense‑Optimized predicts benign; Foldetta predicts benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, the majority of evidence supports a benign impact, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.076542	Structured	0.083482	Uncertain	0.920	0.253	0.000							-10.040	Likely Pathogenic	0.138	Likely Benign	Likely Benign	0.169	Likely Benign	0.1327	0.4439		0.25	Likely Benign	0.0	0.54	Ambiguous	0.40	Likely Benign	0.22	Likely Benign	-2.83	Deleterious	0.985	Probably Damaging	0.533	Possibly Damaging	3.34	Benign	0.01	Affected			0	-1	3.3	16.06
c.2009T>G	L670R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L670R is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. The remaining tools—FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Default—return uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as uncertain. Overall, the majority of reliable predictions indicate a benign effect. There is no ClinVar annotation to contradict this assessment, so the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.161087	Structured	0.090855	Uncertain	0.812	0.385	0.000							-9.801	Likely Pathogenic	0.552	Ambiguous	Likely Benign	0.193	Likely Benign	0.1327	0.1145		0.64	Ambiguous	0.1	1.42	Ambiguous	1.03	Ambiguous	0.67	Ambiguous	-1.74	Neutral	0.993	Probably Damaging	0.755	Possibly Damaging	3.43	Benign	0.41	Tolerated			-3	-2	-8.3	43.03
c.2336G>A	S779N 2D AIThe SynGAP1 missense variant S779N is listed in gnomAD (ID 6‑33442494‑G‑A) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. A high‑accuracy consensus (SGM Consensus) derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN yields a benign majority. The AlphaMissense‑Optimized score is benign, and no Foldetta stability assessment is available. Taken together, the majority of evidence points to a benign impact. This conclusion is consistent with the absence of a ClinVar pathogenic classification, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.509769	Disordered	0.834974	Binding	0.321	0.890	0.375				6-33442494-G-A			-4.880	Likely Benign	0.384	Ambiguous	Likely Benign	0.087	Likely Benign	0.1327	0.4984											-0.75	Neutral	0.021	Benign	0.026	Benign	2.30	Pathogenic	0.23	Tolerated	3.64	6	1	1	-2.7	27.03
c.2768T>C	I923T 2D AIThe SynGAP1 missense variant I923T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, and FATHMM. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as “Uncertain” and the SGM‑Consensus as “Likely Benign”; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.562014	Disordered	0.964857	Binding	0.292	0.852	0.250							-1.180	Likely Benign	0.842	Likely Pathogenic	Ambiguous	0.097	Likely Benign	0.1327	0.1786											-0.53	Neutral	0.837	Possibly Damaging	0.348	Benign	2.73	Benign	0.41	Tolerated			0	-1	-5.2	-12.05
c.3085C>G	Q1029E 2D AIThe SynGAP1 missense variant Q1029E is reported in gnomAD (ID 6‑33443637‑C‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags it as pathogenic, creating a single discordant call. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus itself is benign; Foldetta results are unavailable. Overall, the preponderance of evidence indicates the variant is most likely benign, and this conclusion is not contradicted by any ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.852992	Disordered	0.995643	Binding	0.375	0.734	0.500				6-33443637-C-G	17	1.05e-5	-3.660	Likely Benign	0.281	Likely Benign	Likely Benign	0.044	Likely Benign	0.1327	0.2433											-0.92	Neutral	0.625	Possibly Damaging	0.258	Benign	2.83	Benign	0.26	Tolerated	3.77	5	2	2	0.0	0.98
c.3591G>C	E1197D 2D AIThe SynGAP1 missense variant E1197D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to a likely benign verdict. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (majority vote) also indicates benign. Foldetta stability analysis is unavailable for this residue. Overall, the balance of evidence favors a benign effect for E1197D, and this conclusion does not conflict with any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.613573	Disordered	0.437361	Uncertain	0.827	0.599	0.250							-5.158	Likely Benign	0.776	Likely Pathogenic	Likely Benign	0.348	Likely Benign	0.1327	0.3535											-1.78	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	5.41	Benign	0.16	Tolerated			3	2	0.0	-14.03
c.3591G>T	E1197D 2D AIThe SynGAP1 missense variant E1197D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which is a majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome (3 benign vs. 1 pathogenic). High‑accuracy tools give the following results: AlphaMissense‑Optimized predicts benign; the SGM‑Consensus (majority vote) predicts benign; Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta) has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, and this assessment is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.613573	Disordered	0.437361	Uncertain	0.827	0.599	0.250							-5.158	Likely Benign	0.776	Likely Pathogenic	Likely Benign	0.348	Likely Benign	0.1327	0.3535											-1.78	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	5.41	Benign	0.16	Tolerated			3	2	0.0	-14.03
c.914C>A	T305N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T305N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as tolerated or benign, and the SGM‑Consensus score is “Likely Benign.” Only FATHMM predicts a pathogenic outcome. Stability‑based methods (FoldX, Rosetta, and the combined Foldetta) return uncertain or inconclusive results. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is also benign, and Foldetta remains uncertain. Overall, the majority of evidence supports a benign impact for T305N, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.359901	Structured	0.299706	Uncertain	0.872	0.274	0.125							-3.261	Likely Benign	0.158	Likely Benign	Likely Benign	0.098	Likely Benign	0.1327	0.4352		1.18	Ambiguous	0.2	1.65	Ambiguous	1.42	Ambiguous	0.09	Likely Benign	0.71	Neutral	0.046	Benign	0.040	Benign	2.34	Pathogenic	0.67	Tolerated			0	0	-2.8	13.00
c.1184G>A	G395E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G395E is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only AlphaMissense‑Default predicts a pathogenic outcome, while FoldX and Rosetta give uncertain results. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote) predicts benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. Taken together, the majority of evidence points to a benign effect. There is no ClinVar entry to contradict this conclusion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.513880	Disordered	0.396199	Uncertain	0.474	0.601	0.500							-6.350	Likely Benign	0.594	Likely Pathogenic	Likely Benign	0.310	Likely Benign	0.1328	0.4089		1.60	Ambiguous	0.6	-0.88	Ambiguous	0.36	Likely Benign	0.30	Likely Benign	-1.81	Neutral	0.037	Benign	0.010	Benign	4.25	Benign	0.12	Tolerated			0	-2	-3.1	72.06
c.1610C>T	A537V 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A537V is listed in ClinVar as Benign (ClinVar ID 766762.0) and is present in gnomAD (ID 6‑33438853‑C‑T). Functional prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign; the SGM Consensus, derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, is benign. FoldX alone is uncertain and therefore not considered evidence. Overall, the consensus of available predictions indicates that the variant is most likely benign, in agreement with its ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.116183	Structured	0.037313	Uncertain	0.928	0.362	0.000	Likely Benign		1	6-33438853-C-T	7	4.34e-6	-6.888	Likely Benign	0.120	Likely Benign	Likely Benign	0.382	Likely Benign	0.1328	0.4748		0.54	Ambiguous	0.0	-0.05	Likely Benign	0.25	Likely Benign	0.41	Likely Benign	-1.97	Neutral	0.977	Probably Damaging	0.469	Possibly Damaging	-1.26	Pathogenic	0.24	Tolerated	3.37	35	0	0	2.4	28.05	220.3	-45.1	0.0	0.0	-0.7	0.1						X		Potentially Benign	Ala537 is located on the outer surface of an α-helix (res. Ala533-Val560). The methyl group of Ala537 is on the surface and does not form any interactions. In the variant simulations, the iso-propyl side chain of Val537 is also on the surface, similar to Ala537 in the WT, causing no negative structural effects.
c.1619A>G	Q540R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant Q540R has no ClinVar entry and is present in gnomAD (ID 6‑33438862‑A‑G). Prediction tools that agree on a benign effect include FoldX, Rosetta, Foldetta, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and FATHMM. Two tools report uncertainty: premPS and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as benign. Overall, the majority of evidence points to a benign impact, with only a minority of tools indicating pathogenicity. This conclusion does not contradict ClinVar status, which has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.085092	Structured	0.029522	Uncertain	0.958	0.371	0.000				6-33438862-A-G	1	6.19e-7	-13.312	Likely Pathogenic	0.540	Ambiguous	Likely Benign	0.795	Likely Pathogenic	0.1328	0.1886		-0.06	Likely Benign	0.0	-0.07	Likely Benign	-0.07	Likely Benign	0.88	Ambiguous	-3.98	Deleterious	0.991	Probably Damaging	0.985	Probably Damaging	-1.28	Pathogenic	0.08	Tolerated	3.37	35	1	1	-1.0	28.06
c.3082C>G	L1028V 2D AIThe SynGAP1 missense variant L1028V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign. Foldetta results are not available, so they do not influence the assessment. Overall, the majority of computational evidence indicates that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.899122	Disordered	0.995137	Binding	0.364	0.730	0.500							-3.992	Likely Benign	0.217	Likely Benign	Likely Benign	0.042	Likely Benign	0.1328	0.2715											-0.68	Neutral	0.737	Possibly Damaging	0.376	Benign	2.74	Benign	0.26	Tolerated			2	1	0.4	-14.03
c.3083T>G	L1028R 2D AIThe SynGAP1 missense variant L1028R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign (three benign votes versus one pathogenic). High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.899122	Disordered	0.995137	Binding	0.364	0.730	0.500							-2.204	Likely Benign	0.793	Likely Pathogenic	Ambiguous	0.167	Likely Benign	0.1328	0.1603											-0.24	Neutral	0.960	Probably Damaging	0.761	Possibly Damaging	2.75	Benign	0.84	Tolerated			-3	-2	-8.3	43.03
c.3496G>A	A1166T 2D AIThe SynGAP1 missense variant A1166T is not reported in ClinVar and has no gnomAD entry. Consensus and most in silico predictors classify it as benign: SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized all indicate a benign effect. In contrast, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default predict a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores the variant as benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports Likely Benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect, and this conclusion is not contradicted by ClinVar data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.575842	Disordered	0.811691	Binding	0.381	0.803	0.375							-3.615	Likely Benign	0.748	Likely Pathogenic	Likely Benign	0.343	Likely Benign	0.1328	0.6418											-1.13	Neutral	0.995	Probably Damaging	0.963	Probably Damaging	5.37	Benign	0.26	Tolerated			1	0	-2.5	30.03
c.1156G>A	G386R 2D 3DClick to see structure in 3D Viewer AIClinVar reports no entry for this SynGAP1 G386R variant, and it is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are FoldX, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default, while Rosetta is uncertain. High‑accuracy methods give a benign call from AlphaMissense‑Optimized, a pathogenic result from Foldetta, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive. Overall, the evidence is mixed; the variant is most likely benign, and this assessment does not contradict the ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.733139	Disordered	0.424156	Uncertain	0.334	0.898	0.750							-9.024	Likely Pathogenic	0.709	Likely Pathogenic	Likely Benign	0.453	Likely Benign	0.1329	0.4032		3.62	Destabilizing	2.9	1.07	Ambiguous	2.35	Destabilizing	0.29	Likely Benign	-0.82	Neutral	0.753	Possibly Damaging	0.220	Benign	4.03	Benign	0.01	Affected			-3	-2	-4.1	99.14
c.1156G>C	G386R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G386R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Computational predictors that agree on a benign effect include REVEL, premPS, PROVEAN, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect comprise FoldX, polyPhen‑2 (HumDiv), SIFT, ESM1b, AlphaMissense‑Default, and Foldetta; Rosetta is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta as pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑vs‑2 split. Overall, the balance of evidence favors a pathogenic classification. This conclusion is not contradicted by ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.733139	Disordered	0.424156	Uncertain	0.334	0.898	0.750							-9.024	Likely Pathogenic	0.709	Likely Pathogenic	Likely Benign	0.453	Likely Benign	0.1329	0.4032		3.62	Destabilizing	2.9	1.07	Ambiguous	2.35	Destabilizing	0.29	Likely Benign	-0.82	Neutral	0.753	Possibly Damaging	0.220	Benign	4.03	Benign	0.01	Affected			-3	-2	-4.1	99.14
c.3155G>T	G1052V 2D AIThe SynGAP1 missense variant G1052V is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools cluster around a benign effect: REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all indicate benign, while the high‑accuracy AlphaMissense‑Optimized score is benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign. In contrast, polyPhen‑2 HumDiv and HumVar both predict pathogenic, and ESM1b remains uncertain. No Foldetta stability assessment is available, so it does not influence the overall interpretation. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.984420	Disordered	0.892068	Binding	0.367	0.938	0.875							-7.717	In-Between	0.094	Likely Benign	Likely Benign	0.452	Likely Benign	0.1329	0.3499											-0.12	Neutral	0.901	Possibly Damaging	0.619	Possibly Damaging	3.90	Benign	0.19	Tolerated			-1	-3	4.6	42.08
c.3422C>G	P1141R 2D AIThe SynGAP1 missense variant P1141R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus indicates a likely pathogenic outcome; a Foldetta stability analysis is unavailable. Overall, the majority of computational predictions (seven pathogenic vs. three benign) support a pathogenic classification. This consensus does not contradict any ClinVar annotation, as none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.930790	Disordered	0.716087	Binding	0.364	0.852	1.000							-4.768	Likely Benign	0.626	Likely Pathogenic	Likely Benign	0.120	Likely Benign	0.1329	0.3614											-3.90	Deleterious	0.913	Possibly Damaging	0.690	Possibly Damaging	0.97	Pathogenic	0.00	Affected			0	-2	-2.9	59.07
c.689G>T	C230F 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C230F is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Rosetta, and FATHMM, whereas the majority of tools predict a pathogenic impact: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Foldetta and premPS give uncertain results. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Pathogenic”; Foldetta remains uncertain. Overall, the preponderance of evidence indicates that C230F is most likely pathogenic, and this conclusion does not contradict the ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.268042	Structured	0.308076	Uncertain	0.870	0.308	0.000							-11.134	Likely Pathogenic	0.988	Likely Pathogenic	Likely Pathogenic	0.840	Likely Pathogenic	0.1329	0.4173		-0.09	Likely Benign	0.1	-2.03	Stabilizing	-1.06	Ambiguous	0.51	Ambiguous	-8.73	Deleterious	0.940	Possibly Damaging	0.641	Possibly Damaging	5.96	Benign	0.03	Affected			-4	-2	0.3	44.04
c.1389C>A	D463E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D463E missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and premPS. Only PROVEAN predicts a pathogenic outcome, while Rosetta and AlphaMissense‑Default are uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized scores benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields benign; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, also predicts benign. No prediction or stability result is missing or inconclusive. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.260850	Structured	0.305622	Uncertain	0.940	0.176	0.000							-5.170	Likely Benign	0.527	Ambiguous	Likely Benign	0.162	Likely Benign	0.1330	0.5177		-0.42	Likely Benign	0.1	0.50	Ambiguous	0.04	Likely Benign	0.47	Likely Benign	-2.58	Deleterious	0.012	Benign	0.003	Benign	3.47	Benign	0.29	Tolerated			3	2	0.0	14.03
c.1389C>G	D463E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D463E missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and premPS. Only PROVEAN predicts a pathogenic outcome, while Rosetta and AlphaMissense‑Default are uncertain. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) resolves to benign, and Foldetta also indicates benign stability. No prediction or stability result is missing or inconclusive. Overall, the variant is most likely benign based on the collective evidence, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.260850	Structured	0.305622	Uncertain	0.940	0.176	0.000							-5.170	Likely Benign	0.527	Ambiguous	Likely Benign	0.162	Likely Benign	0.1330	0.5177		-0.42	Likely Benign	0.1	0.50	Ambiguous	0.04	Likely Benign	0.47	Likely Benign	-2.58	Deleterious	0.012	Benign	0.003	Benign	3.47	Benign	0.29	Tolerated			3	2	0.0	14.03
c.151A>G	I51V 2D AIThe SynGAP1 missense variant I51V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect. The variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.291804	Structured	0.454181	Uncertain	0.606	0.710	0.000							-3.397	Likely Benign	0.195	Likely Benign	Likely Benign	0.065	Likely Benign	0.1330	0.3602											-0.24	Neutral	0.004	Benign	0.007	Benign	4.26	Benign	0.00	Affected			4	3	-0.3	-14.03
c.1846G>C	D616H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D616H missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM. Those that agree on a pathogenic effect comprise SGM‑Consensus, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default. Two tools give uncertain results—Rosetta and AlphaMissense‑Optimized—so their outputs are treated as unavailable for inference. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) is Pathogenic. Overall, the majority of evidence points to a pathogenic effect. The variant’s predicted pathogenicity does not contradict ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.129801	Structured	0.166689	Uncertain	0.867	0.252	0.000							-9.815	Likely Pathogenic	0.904	Likely Pathogenic	Ambiguous	0.316	Likely Benign	0.1330	0.4273		2.13	Destabilizing	0.2	1.89	Ambiguous	2.01	Destabilizing	0.45	Likely Benign	-5.57	Deleterious	0.999	Probably Damaging	0.952	Probably Damaging	3.30	Benign	0.03	Affected			1	-1	0.3	22.05
c.335G>A	G112E 2D AIThe SynGAP1 missense variant G112E is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized result is uncertain, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split; Foldetta predictions are not available. Overall, the majority of evidence (five benign vs. three pathogenic) supports a benign classification. This conclusion does not contradict ClinVar status, as the variant has no ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.728858	Disordered	0.640153	Binding	0.332	0.867	0.750							-3.470	Likely Benign	0.818	Likely Pathogenic	Ambiguous	0.134	Likely Benign	0.1330	0.3814											-3.30	Deleterious	0.421	Benign	0.146	Benign	3.96	Benign	0.00	Affected			0	-2	-3.1	72.06
c.3749A>G	Q1250R 2D AIThe SynGAP1 missense variant Q1250R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.759478	Disordered	0.360484	Uncertain	0.881	0.554	0.750							-5.183	Likely Benign	0.230	Likely Benign	Likely Benign	0.148	Likely Benign	0.1330	0.0874											0.76	Neutral	0.994	Probably Damaging	0.988	Probably Damaging	3.09	Benign	1.00	Tolerated			1	1	-1.0	28.06
c.211G>A	D71N 2D AIThe SynGAP1 D71N missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also reports Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect. The variant is most likely benign, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.575842	Disordered	0.456046	Uncertain	0.350	0.799	0.375							-4.279	Likely Benign	0.370	Ambiguous	Likely Benign	0.136	Likely Benign	0.1331	0.6021											-1.25	Neutral	0.198	Benign	0.021	Benign	4.08	Benign	0.00	Affected			2	1	0.0	-0.98
c.2959G>A	D987N 2D AIThe SynGAP1 D987N missense variant is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 benign vs 2 pathogenic), and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.823549	Disordered	0.919118	Binding	0.299	0.903	0.750							-5.035	Likely Benign	0.698	Likely Pathogenic	Likely Benign	0.126	Likely Benign	0.1331	0.7427											-1.42	Neutral	0.943	Possibly Damaging	0.755	Possibly Damaging	2.41	Pathogenic	0.49	Tolerated			2	1	0.0	-0.98
c.3802C>G	L1268V 2D AIThe SynGAP1 missense variant L1268V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags the variant as pathogenic, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also reports likely benign. Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for the variant, and this conclusion is not contradicted by any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.458154	Structured	0.804315	Binding	0.859	0.629	0.000							-4.137	Likely Benign	0.109	Likely Benign	Likely Benign	0.056	Likely Benign	0.1331	0.2289											-0.24	Neutral	0.649	Possibly Damaging	0.157	Benign	2.73	Benign	0.25	Tolerated			2	1	0.4	-14.03
c.2015C>T	T672M 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant T672M is listed in ClinVar with an uncertain significance and is present in gnomAD (ID 6‑33441274‑C‑T). Prediction tools that classify the variant as benign include REVEL, FoldX, premPS, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. Rosetta and Foldetta report uncertain results, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while SGM Consensus and Foldetta remain unavailable. Overall, the balance of evidence favors a benign effect, and this conclusion does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.116183	Structured	0.102069	Uncertain	0.586	0.362	0.000	Conflicting		3	6-33441274-C-T	19	1.18e-5	-9.472	Likely Pathogenic	0.174	Likely Benign	Likely Benign	0.127	Likely Benign	0.1332	0.6677		0.31	Likely Benign	0.4	1.52	Ambiguous	0.92	Ambiguous	0.41	Likely Benign	-4.34	Deleterious	0.993	Probably Damaging	0.520	Possibly Damaging	3.39	Benign	0.00	Affected	3.40	25	-1	-1	2.6	30.09	231.9	-52.9	1.1	0.1	0.5	0.0		X				X		Potentially Pathogenic	The hydroxyl group of Thr672, located in an entangled α-α loop connecting the two α-helices (res. Ser641-Glu666 and res. Leu685-Val699), is involved in a highly coordinated hydrogen-bonding network between residues from two α-helices (res. Ser641-Glu666 and res. Arg563-Glu578) and from the α-α loop itself, such as Lys566, Glu666, and Asn669. Met672 can only form a hydrogen bond with the amino group of the Lys566 side chain via its backbone carbonyl group. Nevertheless, the Lys566-Glu666 salt bridge forms intermittently. This is possible because Asn669 keeps the carboxylate group of Glu666 in the vicinity through hydrogen bonding, and the hydrophobic side chain of Met stays mostly rotated away from the salt bridge. Consequently, no drastic disruption of the hydrogen-bond network that keeps the loop close to the helices occurs in the variant simulations.
c.2194A>T	R732W 2D AIThe SynGAP1 missense variant R732W is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, five tools predict pathogenicity versus four predicting benign, with no ClinVar evidence to contradict these computational findings. Thus, the variant is most likely pathogenic based on the current predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.846163	Disordered	0.412403	Uncertain	0.427	0.673	0.750							-11.976	Likely Pathogenic	0.252	Likely Benign	Likely Benign	0.161	Likely Benign	0.1332	0.2748											-3.57	Deleterious	1.000	Probably Damaging	0.973	Probably Damaging	2.53	Benign	0.01	Affected			2	-3	3.6	30.03
c.3075G>C	Q1025H 2D AIThe SynGAP1 missense variant Q1025H is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Prediction tools largely agree on a benign effect: SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the variant as benign. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence supports a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.879233	Disordered	0.993410	Binding	0.363	0.746	0.500							-4.976	Likely Benign	0.405	Ambiguous	Likely Benign	0.051	Likely Benign	0.1332	0.3852											-1.43	Neutral	0.014	Benign	0.012	Benign	2.68	Benign	0.05	Affected			3	0	0.3	9.01
c.3075G>T	Q1025H 2D AIThe SynGAP1 missense variant Q1025H is not reported in ClinVar and is absent from gnomAD, indicating no known population frequency data. Prediction tools largely agree on a benign effect: SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the variant as benign. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence supports a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.879233	Disordered	0.993410	Binding	0.363	0.746	0.500							-4.976	Likely Benign	0.405	Ambiguous	Likely Benign	0.051	Likely Benign	0.1332	0.3852											-1.43	Neutral	0.014	Benign	0.012	Benign	2.68	Benign	0.05	Affected			3	0	0.3	9.01
c.1526C>T	A509V 2D 3DClick to see structure in 3D Viewer AISynGAP1 A509V is not reported in ClinVar and is absent from gnomAD. High‑accuracy predictors give mixed results: AlphaMissense‑Optimized classifies the variant as benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels it pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, is inconclusive because FoldX is uncertain and Rosetta is benign. Among the remaining tools, benign predictions come from REVEL, Rosetta, premPS, polyPhen2_HumDiv, polyPhen2_HumVar, and SIFT, whereas pathogenic predictions come from SGM‑Consensus, PROVEAN, ESM1b, and FATHMM. AlphaMissense‑Default and FoldX remain uncertain. Overall, the majority of evidence points toward a benign effect, and this assessment does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.250110	Uncertain	0.923	0.256	0.000							-11.987	Likely Pathogenic	0.382	Ambiguous	Likely Benign	0.474	Likely Benign	0.1333	0.5706		0.52	Ambiguous	0.5	0.35	Likely Benign	0.44	Likely Benign	-0.25	Likely Benign	-3.11	Deleterious	0.064	Benign	0.048	Benign	-1.15	Pathogenic	0.18	Tolerated			0	0	2.4	28.05
c.1649C>A	A550D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A550D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect. Benign predictions: none. Pathogenic predictions: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized. Uncertain predictions: Rosetta and Foldetta. High‑accuracy assessments further support a damaging outcome: AlphaMissense‑Optimized is pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, remains uncertain. Overall, the overwhelming majority of evidence indicates a pathogenic effect. Based on the aggregate predictions, the variant is most likely pathogenic, and this is not contradicted by ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.018106	Structured	0.007241	Uncertain	0.954	0.265	0.000							-18.844	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.879	Likely Pathogenic	0.1333	0.1783		2.51	Destabilizing	0.1	1.46	Ambiguous	1.99	Ambiguous	1.01	Destabilizing	-5.43	Deleterious	0.999	Probably Damaging	0.971	Probably Damaging	-1.32	Pathogenic	0.01	Affected			0	-2	-5.3	44.01
c.1898T>A	L633Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L633Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only FATHMM, whereas all other evaluated algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy methods further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the overwhelming consensus of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because the variant is not yet catalogued in ClinVar. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.045352	Structured	0.045407	Uncertain	0.952	0.252	0.000							-14.303	Likely Pathogenic	0.993	Likely Pathogenic	Likely Pathogenic	0.712	Likely Pathogenic	0.1333	0.0876		2.98	Destabilizing	0.1	2.97	Destabilizing	2.98	Destabilizing	2.23	Destabilizing	-5.98	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.69	Benign	0.00	Affected			-2	-2	-7.3	14.97
c.2344G>C	D782H 2D AIThe SynGAP1 missense variant D782H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely converge on a deleterious effect: pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). Only REVEL predicts a benign outcome, while AlphaMissense‑Optimized is uncertain. High‑accuracy assessments show the SGM‑Consensus as Likely Pathogenic, whereas AlphaMissense‑Optimized remains inconclusive and Foldetta data are unavailable. Taken together, the majority of evidence supports a pathogenic interpretation, and this is consistent with the absence of a ClinVar assertion. Therefore, the variant is most likely pathogenic, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.604312	Disordered	0.768342	Binding	0.285	0.883	0.625							-8.528	Likely Pathogenic	0.937	Likely Pathogenic	Ambiguous	0.311	Likely Benign	0.1333	0.7286											-2.63	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	1.93	Pathogenic	0.00	Affected			1	-1	0.3	22.05
c.3259T>A	S1087T 2D AIThe SynGAP1 missense variant S1087T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to the variant being most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.912647	Disordered	0.974805	Binding	0.357	0.891	1.000							-4.455	Likely Benign	0.128	Likely Benign	Likely Benign	0.044	Likely Benign	0.1333	0.6503											-1.01	Neutral	0.790	Possibly Damaging	0.266	Benign	2.66	Benign	0.25	Tolerated			1	1	0.1	14.03
c.3305C>T	A1102V 2D AIThe SynGAP1 missense variant A1102V is listed in ClinVar (ID 2846719.0) as Benign and is present in gnomAD (variant ID 6‑33443857‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). Only FATHMM predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion aligns with the ClinVar benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.915074	Disordered	0.962659	Binding	0.388	0.859	0.875	Benign		1	6-33443857-C-T			-2.440	Likely Benign	0.077	Likely Benign	Likely Benign	0.081	Likely Benign	0.1333	0.6264											-1.27	Neutral	0.017	Benign	0.028	Benign	2.29	Pathogenic	0.12	Tolerated	3.77	5	0	0	2.4	28.05
c.3338G>T	G1113V 2D AIThe SynGAP1 missense variant G1113V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. The variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar claim exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.905695	Disordered	0.900456	Binding	0.327	0.910	0.875							-5.708	Likely Benign	0.093	Likely Benign	Likely Benign	0.088	Likely Benign	0.1333	0.4224											-1.98	Neutral	0.827	Possibly Damaging	0.456	Possibly Damaging	2.53	Benign	0.11	Tolerated			-1	-3	4.6	42.08
c.1627C>G	L543V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L543V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—classify the variant as pathogenic. AlphaMissense‑Optimized is inconclusive (uncertain). High‑accuracy assessments further support pathogenicity: the SGM‑Consensus predicts “Likely Pathogenic,” and Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts a destabilizing, pathogenic effect. AlphaMissense‑Optimized remains uncertain. Based on the overwhelming majority of predictions, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.048328	Structured	0.020918	Uncertain	0.963	0.314	0.000							-11.561	Likely Pathogenic	0.908	Likely Pathogenic	Ambiguous	0.398	Likely Benign	0.1334	0.2028		3.09	Destabilizing	0.3	2.03	Destabilizing	2.56	Destabilizing	1.28	Destabilizing	-2.99	Deleterious	0.998	Probably Damaging	0.992	Probably Damaging	1.99	Pathogenic	0.01	Affected			2	1	0.4	-14.03
c.1829T>G	L610R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L610R is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess pathogenicity are unanimous: SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic. No tool in the dataset predicts a benign effect. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized reports a pathogenic outcome; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, predicts a pathogenic impact. Consequently, the variant is most likely pathogenic based on the available predictions, and this assessment does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.209504	Uncertain	0.888	0.253	0.000							-13.855	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	0.949	Likely Pathogenic	0.1334	0.0615		5.14	Destabilizing	0.5	4.60	Destabilizing	4.87	Destabilizing	1.89	Destabilizing	-5.94	Deleterious	0.998	Probably Damaging	0.998	Probably Damaging	-1.58	Pathogenic	0.00	Affected			-3	-2	-8.3	43.03
c.268G>C	V90L 2D AIThe SynGAP1 missense variant V90L is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, while SIFT uniquely predicts it as pathogenic. The consensus from the SGM framework, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a Likely Benign verdict. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports a benign outcome, the SGM Consensus also indicates Likely Benign, and Foldetta data are unavailable. With the majority of evidence pointing to a benign effect and no conflicting ClinVar annotation, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.570702	Disordered	0.542047	Binding	0.343	0.873	0.500							-3.676	Likely Benign	0.522	Ambiguous	Likely Benign	0.056	Likely Benign	0.1334	0.4487											-0.24	Neutral	0.103	Benign	0.015	Benign	4.02	Benign	0.00	Affected			2	1	-0.4	14.03
c.268G>T	V90L 2D AIThe SynGAP1 missense variant V90L is not reported in ClinVar and has no entries in gnomAD, indicating it is not catalogued in these databases. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, SGM‑Consensus indicates Likely Benign, and Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign effect for V90L, and this conclusion does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.570702	Disordered	0.542047	Binding	0.343	0.873	0.500							-3.676	Likely Benign	0.522	Ambiguous	Likely Benign	0.056	Likely Benign	0.1334	0.4487											-0.24	Neutral	0.103	Benign	0.015	Benign	4.02	Benign	0.00	Affected			2	1	-0.4	14.03
c.3386T>G	L1129R 2D AIThe SynGAP1 missense variant L1129R is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.903857	Disordered	0.876543	Binding	0.339	0.909	0.875							-2.613	Likely Benign	0.442	Ambiguous	Likely Benign	0.376	Likely Benign	0.1334	0.1636											-1.68	Neutral	0.005	Benign	0.007	Benign	5.48	Benign	0.00	Affected			-3	-2	-8.3	43.03
c.3676C>A	Q1226K 2D AIThe SynGAP1 missense variant Q1226K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—all predict a pathogenic impact. AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. High‑accuracy evidence therefore points to a likely pathogenic outcome: AlphaMissense‑Optimized is inconclusive, SGM‑Consensus indicates likely pathogenic, and Foldetta data are missing. Consequently, the variant is most likely pathogenic based on the collective predictions, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.529623	Disordered	0.432206	Uncertain	0.850	0.547	0.250							-13.233	Likely Pathogenic	0.890	Likely Pathogenic	Ambiguous	0.212	Likely Benign	0.1334	0.3199											-3.16	Deleterious	0.985	Probably Damaging	0.981	Probably Damaging	1.82	Pathogenic	0.00	Affected			1	1	-0.4	0.04
c.928G>C	E310Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E310Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign are Rosetta and Foldetta, whereas the remaining tools—REVEL, SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—predict pathogenicity. FoldX and premPS give uncertain results. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized reports a pathogenic effect; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates Likely Pathogenic; Foldetta, a protein‑folding stability approach combining FoldX‑MD and Rosetta, predicts a benign outcome. Overall, the majority of evidence points to a pathogenic impact, and this assessment does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.222385	Structured	0.346136	Uncertain	0.914	0.337	0.125							-11.093	Likely Pathogenic	0.981	Likely Pathogenic	Likely Pathogenic	0.688	Likely Pathogenic	0.1334	0.8341		1.16	Ambiguous	0.5	-0.38	Likely Benign	0.39	Likely Benign	0.85	Ambiguous	-2.76	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	1.24	Pathogenic	0.01	Affected			2	2	0.0	-0.98
c.1123G>A	G375R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G375R is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify the variant as benign include REVEL, premPS, PROVEAN, SIFT, and AlphaMissense‑Optimized, whereas tools that predict pathogenicity are FoldX, Rosetta, Foldetta, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Overall, the majority of predictions (7 pathogenic vs. 5 benign) indicate a likely pathogenic effect, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.604312	Disordered	0.428340	Uncertain	0.301	0.836	0.625							-8.955	Likely Pathogenic	0.609	Likely Pathogenic	Likely Benign	0.497	Likely Benign	0.1335	0.4513		2.97	Destabilizing	1.3	12.66	Destabilizing	7.82	Destabilizing	0.36	Likely Benign	-1.15	Neutral	0.845	Possibly Damaging	0.523	Possibly Damaging	1.32	Pathogenic	0.11	Tolerated			-3	-2	-4.1	99.14
c.1123G>C	G375R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G375R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, premPS, PROVEAN, SIFT, and AlphaMissense‑Optimized; pathogenic predictions come from FoldX, Rosetta, Foldetta, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts benign, whereas Foldetta indicates a destabilizing, pathogenic change, and the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as likely pathogenic. Overall, the majority of evidence points to a pathogenic impact, and this conclusion does not conflict with the absence of a ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.604312	Disordered	0.428340	Uncertain	0.301	0.836	0.625							-8.955	Likely Pathogenic	0.609	Likely Pathogenic	Likely Benign	0.497	Likely Benign	0.1335	0.4513		2.97	Destabilizing	1.3	12.66	Destabilizing	7.82	Destabilizing	0.36	Likely Benign	-1.15	Neutral	0.845	Possibly Damaging	0.523	Possibly Damaging	1.32	Pathogenic	0.11	Tolerated			-3	-2	-4.1	99.14
c.1195G>A	A399T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A399T is listed in ClinVar (ID 1990638.0) as Benign and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; the only inconclusive results come from FoldX, Rosetta, and Foldetta, which are treated as unavailable evidence. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign, and Foldetta as Uncertain. Overall, the variant is most likely benign, and this conclusion aligns with its ClinVar benign classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.394753	Structured	0.407674	Uncertain	0.939	0.490	0.125	Benign		1				-5.236	Likely Benign	0.114	Likely Benign	Likely Benign	0.272	Likely Benign	0.1335	0.6477		1.24	Ambiguous	0.1	0.91	Ambiguous	1.08	Ambiguous	0.49	Likely Benign	-0.40	Neutral	0.131	Benign	0.039	Benign	5.41	Benign	0.69	Tolerated	3.38	26	1	0	-2.5	30.03	211.4	-41.4	0.0	0.0	0.6	0.4		X						Potentially Pathogenic	The methyl group of Ala399, located in an anti-parallel β sheet strand (res. Ala399-Ile411), is swapped for a hydroxyl-containing threonine. In the variant simulations, the hydroxyl group of Thr399 can form H-bonds with the backbone atoms of the residues in the membrane-facing loops (e.g., Gly382) in the C2 domain. Consequently, the ability of the Thr399 side chain to form H-bonds with the membrane-facing loops could adversely affect the dynamics and stability of the SynGAP-membrane association. However, since the effects on the dynamics of the membrane-facing loops can only be studied through the SynGAP-membrane complex, no definite conclusions can be drawn.
c.3071T>G	L1024R 2D AIThe SynGAP1 missense variant L1024R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b, whereas those that agree on a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy AlphaMissense‑Optimized tool returns an uncertain result, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of available predictions (5 pathogenic vs. 3 benign) lean toward a pathogenic interpretation. This assessment does not contradict ClinVar status, as the variant is not yet catalogued there. Thus, based on current computational evidence, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.862302	Disordered	0.992699	Binding	0.327	0.753	0.500							-3.434	Likely Benign	0.841	Likely Pathogenic	Ambiguous	0.148	Likely Benign	0.1335	0.1557											-2.41	Neutral	0.997	Probably Damaging	0.962	Probably Damaging	2.40	Pathogenic	0.02	Affected			-3	-2	-8.3	43.03
c.3628C>A	H1210N 2D AIThe SynGAP1 missense variant H1210N is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only two tools—polyPhen‑2 HumDiv and SIFT—suggest a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are not available, so they do not influence the assessment. Overall, the consensus of available predictions indicates that H1210N is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.599170	Disordered	0.587579	Binding	0.900	0.567	0.375							-5.022	Likely Benign	0.175	Likely Benign	Likely Benign	0.041	Likely Benign	0.1335	0.2030											-1.48	Neutral	0.468	Possibly Damaging	0.206	Benign	2.71	Benign	0.05	Affected			2	1	-0.3	-23.04
c.520A>C	M174L 2D AIThe SynGAP1 missense variant M174L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Taken together, the majority of evidence points to a benign impact for M174L. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing clinical classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.485854	Uncertain	0.373	0.620	0.375							-5.839	Likely Benign	0.608	Likely Pathogenic	Likely Benign	0.192	Likely Benign	0.1335	0.4545											-0.82	Neutral	0.055	Benign	0.011	Benign	4.21	Benign	0.46	Tolerated			4	2	1.9	-18.03
c.520A>T	M174L 2D AIThe SynGAP1 missense variant M174L is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Taken together, the majority of evidence points to a benign impact for M174L. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing clinical classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.661982	Disordered	0.485854	Uncertain	0.373	0.620	0.375							-5.839	Likely Benign	0.608	Likely Pathogenic	Likely Benign	0.192	Likely Benign	0.1335	0.4545											-0.82	Neutral	0.055	Benign	0.011	Benign	4.21	Benign	0.46	Tolerated			4	2	1.9	-18.03
c.541C>A	H181N 2D AIThe SynGAP1 missense variant H181N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and ESM1b, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign prediction (2 benign vs. 1 pathogenic). Foldetta results are unavailable. Overall, the preponderance of evidence indicates that H181N is most likely benign, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.505461	Disordered	0.439530	Uncertain	0.294	0.616	0.500							-10.315	Likely Pathogenic	0.526	Ambiguous	Likely Benign	0.090	Likely Benign	0.1335	0.1839											-1.50	Neutral	0.421	Benign	0.107	Benign	4.18	Benign	0.05	Affected			2	1	-0.3	-23.04
c.641T>G	L214R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L214R missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, whereas the majority of tools (SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; FoldX, Rosetta, and Foldetta are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as uncertain. Overall, the evidence strongly favors a pathogenic effect for this variant, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.155435	Structured	0.372604	Uncertain	0.818	0.302	0.125							-11.458	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	0.927	Likely Pathogenic	0.1335	0.0772		1.35	Ambiguous	0.6	0.92	Ambiguous	1.14	Ambiguous	1.68	Destabilizing	-4.98	Deleterious	0.997	Probably Damaging	0.916	Probably Damaging	5.75	Benign	0.00	Affected			-3	-2	-8.3	43.03
c.1547C>T	A516V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A516V missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that assess the variant’s effect fall into two groups: benign predictions come from FoldX, Rosetta, and SIFT, while pathogenic predictions are made by SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; premPS is uncertain. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely pathogenic, whereas Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign. Overall, the majority of tools, including the high‑accuracy predictors, lean toward a pathogenic effect. This conclusion is not contradicted by ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.167423	Uncertain	0.938	0.284	0.000							-11.545	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	0.639	Likely Pathogenic	0.1336	0.5263		0.42	Likely Benign	0.1	0.16	Likely Benign	0.29	Likely Benign	0.62	Ambiguous	-3.61	Deleterious	0.999	Probably Damaging	0.988	Probably Damaging	-1.32	Pathogenic	0.09	Tolerated			0	0	2.4	28.05
c.2213G>C	S738T 2D AIThe SynGAP1 missense variant S738T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the variant as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as likely benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of all available predictions is that the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.812494	Disordered	0.441162	Uncertain	0.284	0.827	0.875							-3.926	Likely Benign	0.062	Likely Benign	Likely Benign	0.039	Likely Benign	0.1336	0.4227											-0.68	Neutral	0.010	Benign	0.010	Benign	2.73	Benign	0.51	Tolerated			1	1	0.1	14.03
c.1051G>A	A351T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A351T missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that uniformly indicate a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and FATHMM. Uncertain predictions come from Rosetta and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely benign, and Foldetta as inconclusive. Overall, the majority of evidence supports a benign impact for A351T, and this conclusion does not contradict the ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.216401	Structured	0.362025	Uncertain	0.925	0.342	0.000							-6.863	Likely Benign	0.077	Likely Benign	Likely Benign	0.040	Likely Benign	0.1337	0.6713		0.22	Likely Benign	0.0	0.80	Ambiguous	0.51	Ambiguous	0.49	Likely Benign	-2.42	Neutral	0.524	Possibly Damaging	0.138	Benign	1.71	Pathogenic	0.06	Tolerated			1	0	-2.5	30.03
c.1973G>T	G658V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G658V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, premPS, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, polyPhen‑2 HumVar, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are PROVEAN and polyPhen‑2 HumDiv; Rosetta’s output is uncertain and therefore not used as evidence. High‑accuracy assessments show AlphaMissense‑Optimized as Benign, the SGM‑Consensus as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta) as Benign. Taken together, the majority of reliable predictors indicate a benign impact. Thus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.029376	Structured	0.180299	Uncertain	0.942	0.251	0.000							-6.815	Likely Benign	0.166	Likely Benign	Likely Benign	0.117	Likely Benign	0.1337	0.3330		-0.07	Likely Benign	0.0	-0.71	Ambiguous	-0.39	Likely Benign	0.34	Likely Benign	-3.23	Deleterious	0.841	Possibly Damaging	0.264	Benign	3.38	Benign	0.13	Tolerated			-1	-3	4.6	42.08
c.1978A>C	M660L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M660L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, FATHMM, polyPhen‑2 HumVar, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. No predictions are missing or inconclusive. Overall, the balance of evidence leans toward a benign classification, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.047319	Structured	0.134270	Uncertain	0.944	0.289	0.000							-12.576	Likely Pathogenic	0.766	Likely Pathogenic	Likely Benign	0.330	Likely Benign	0.1337	0.3891		0.16	Likely Benign	0.0	-0.10	Likely Benign	0.03	Likely Benign	0.97	Ambiguous	-2.99	Deleterious	0.596	Possibly Damaging	0.101	Benign	3.56	Benign	0.03	Affected			4	2	1.9	-18.03
c.1978A>T	M660L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M660L is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, FATHMM, polyPhen‑2 HumVar, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. No predictions are missing or inconclusive. Overall, the balance of evidence leans toward a benign classification, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.047319	Structured	0.134270	Uncertain	0.944	0.289	0.000							-12.576	Likely Pathogenic	0.766	Likely Pathogenic	Likely Benign	0.330	Likely Benign	0.1337	0.3891		0.16	Likely Benign	0.0	-0.10	Likely Benign	0.03	Likely Benign	0.97	Ambiguous	-2.99	Deleterious	0.596	Possibly Damaging	0.101	Benign	3.56	Benign	0.03	Affected			4	2	1.9	-18.03
c.3860C>G	P1287R 2D AIThe SynGAP1 missense variant P1287R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign status. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign effect for P1287R, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.827927	Disordered	0.813701	Binding	0.538	0.777	0.750							-2.180	Likely Benign	0.165	Likely Benign	Likely Benign	0.054	Likely Benign	0.1337	0.2427											-1.37	Neutral	0.586	Possibly Damaging	0.172	Benign	2.77	Benign	0.01	Affected			0	-2	-2.9	59.07
c.1802C>T	A601V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A601V is listed in ClinVar (ID 968190.0) with an uncertain clinical significance and is not reported in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from Rosetta and FATHMM, while pathogenic predictions are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus score. Four tools (FoldX, Foldetta, premPS, AlphaMissense‑Optimized) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as uncertain. Overall, the majority of evidence points to a pathogenic effect, which is consistent with the ClinVar designation of uncertain significance rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.008895	Structured	0.174517	Uncertain	0.955	0.156	0.000	Uncertain		1				-10.447	Likely Pathogenic	0.853	Likely Pathogenic	Ambiguous	0.535	Likely Pathogenic	0.1338	0.5263		1.64	Ambiguous	0.1	0.35	Likely Benign	1.00	Ambiguous	0.81	Ambiguous	-3.98	Deleterious	1.000	Probably Damaging	0.989	Probably Damaging	2.74	Benign	0.03	Affected	3.37	35	0	0	2.4	28.05	228.5	-45.5	0.0	0.0	0.4	0.5						X		Potentially Benign	The methyl side chain of Ala601, located on an α helix (res. Glu582-Met603), packs hydrophobically against other hydrophobic residues in the inter-helix space (e.g., Phe597, Leu598, Leu506, Phe608).In the variant simulations, Val601, which has similar size and physicochemical properties to alanine, resides in the inter-helix hydrophobic space in a similar manner to Ala601 in the WT, causing no apparent negative effect on the protein structure. However, the effect of the residue swap on the SynGAP-Ras complex formation or GTPase activation cannot be fully addressed using the SynGAP solvent-only simulations.
c.2276T>A	M759K 2D AIThe SynGAP1 missense variant M759K (ClinVar ID 4178662) is listed as ClinVar status Uncertain and is not present in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as Likely Benign; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, which does not contradict the ClinVar Uncertain designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.525368	Disordered	0.879389	Binding	0.299	0.864	0.375	Uncertain		1				-5.670	Likely Benign	0.616	Likely Pathogenic	Likely Benign	0.288	Likely Benign	0.1338	0.0688											-1.86	Neutral	0.891	Possibly Damaging	0.492	Possibly Damaging	2.55	Benign	0.06	Tolerated			0	-1	-5.8	-3.02
c.245T>G	L82R 2D AIThe SynGAP1 missense variant L82R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely benign outcome; Foldetta results are unavailable. Overall, the majority of predictions (six benign vs. four pathogenic) lean toward a benign interpretation, and this is not contradicted by any ClinVar annotation. Thus, based on the current computational evidence, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.637480	Disordered	0.517720	Binding	0.284	0.890	0.375							-6.345	Likely Benign	0.974	Likely Pathogenic	Likely Pathogenic	0.077	Likely Benign	0.1338	0.0590											-2.18	Neutral	0.939	Possibly Damaging	0.114	Benign	3.67	Benign	0.00	Affected			-3	-2	-8.3	43.03
c.859G>A	D287N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D287N missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools cluster into two groups: benign predictions (REVEL, FoldX, premPS, SIFT) and pathogenic predictions (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default). Two tools give uncertain results (Rosetta, AlphaMissense‑Optimized). High‑accuracy assessments further separate the evidence: AlphaMissense‑Optimized is uncertain; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates a likely pathogenic effect; Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, predicts a benign impact. Overall, the majority of conventional predictors lean toward pathogenicity, while the most accurate stability‑based method suggests benign. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.102787	Structured	0.389029	Uncertain	0.912	0.268	0.000							-10.167	Likely Pathogenic	0.944	Likely Pathogenic	Ambiguous	0.372	Likely Benign	0.1338	0.8194		0.16	Likely Benign	0.3	-0.54	Ambiguous	-0.19	Likely Benign	0.05	Likely Benign	-4.60	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.62	Pathogenic	0.06	Tolerated			2	1	0.0	-0.98
c.1141G>A	G381R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G381R is not reported in ClinVar and is present in gnomAD (ID 6‑33438046‑G‑A). Prediction tools that classify it as benign include premPS, PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that predict pathogenicity are SGM‑Consensus, REVEL, FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized indicates a benign outcome, whereas the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta) both predict pathogenicity. Overall, the majority of evidence points to a pathogenic impact for G381R, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.724957	Disordered	0.431692	Uncertain	0.301	0.951	0.750				6-33438046-G-A			-8.990	Likely Pathogenic	0.652	Likely Pathogenic	Likely Benign	0.589	Likely Pathogenic	0.1339	0.3945		5.60	Destabilizing	0.9	2.80	Destabilizing	4.20	Destabilizing	0.20	Likely Benign	-0.82	Neutral	0.985	Probably Damaging	0.795	Possibly Damaging	1.32	Pathogenic	0.08	Tolerated	4.32	9	-2	-3	-4.1	99.14
c.1141G>C	G381R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G381R is catalogued in gnomAD (ID 6‑33438046‑G‑C) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from premPS, PROVEAN, SIFT, and AlphaMissense‑Optimized; pathogenic predictions arise from SGM‑Consensus, REVEL, FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized reports a benign outcome, whereas the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) and Foldetta (combining FoldX‑MD and Rosetta) both predict pathogenicity. Overall, the majority of evidence indicates a pathogenic impact for G381R, and this conclusion is not contradicted by ClinVar status, which currently lacks an entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.724957	Disordered	0.431692	Uncertain	0.301	0.951	0.750				6-33438046-G-C	2	1.25e-6	-8.990	Likely Pathogenic	0.652	Likely Pathogenic	Likely Benign	0.589	Likely Pathogenic	0.1339	0.3945		5.60	Destabilizing	0.9	2.80	Destabilizing	4.20	Destabilizing	0.20	Likely Benign	-0.82	Neutral	0.985	Probably Damaging	0.795	Possibly Damaging	1.32	Pathogenic	0.08	Tolerated	4.32	9	-2	-3	-4.1	99.14
c.3035C>G	P1012R 2D AIThe SynGAP1 missense variant P1012R is not reported in ClinVar and is absent from gnomAD, indicating no documented population frequency. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” verdict. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, is not available for this variant. Overall, the consensus of all available predictions strongly supports a benign classification, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.834292	Disordered	0.894674	Binding	0.319	0.866	0.625							-4.413	Likely Benign	0.104	Likely Benign	Likely Benign	0.034	Likely Benign	0.1339	0.3083											1.24	Neutral	0.000	Benign	0.002	Benign	2.89	Benign	0.88	Tolerated			0	-2	-2.9	59.07
c.3502A>G	I1168V 2D AIThe SynGAP1 missense variant I1168V is listed in ClinVar (ID 936001.0) with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PolyPhen‑2 HumDiv and PolyPhen‑2 HumVar. AlphaMissense‑Default is uncertain, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports a “Likely Benign” outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this consensus does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.642678	Disordered	0.763262	Binding	0.423	0.796	0.500	Uncertain		1				-3.263	Likely Benign	0.524	Ambiguous	Likely Benign	0.363	Likely Benign	0.1339	0.4374											-0.14	Neutral	0.876	Possibly Damaging	0.643	Possibly Damaging	5.47	Benign	0.84	Tolerated	3.88	3	4	3	-0.3	-14.03
c.3839T>G	M1280R 2D AIThe SynGAP1 missense variant M1280R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for M1280R, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.882776	Disordered	0.822030	Binding	0.510	0.726	0.875							-2.347	Likely Benign	0.209	Likely Benign	Likely Benign	0.272	Likely Benign	0.1339	0.0837											-1.97	Neutral	0.001	Benign	0.001	Benign	2.44	Pathogenic	0.00	Affected			0	-1	-6.4	24.99
c.391G>T	G131C 2D AIThe SynGAP1 missense variant G131C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include REVEL, FATHMM, and AlphaMissense‑Optimized, whereas those that predict pathogenicity are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, while the SGM Consensus again indicates Likely Pathogenic; the Foldetta protein‑folding stability analysis is unavailable for this variant. Overall, the majority of tools predict pathogenicity, and this aligns with the SGM Consensus. Therefore, the variant is most likely pathogenic based on the available predictions, and this conclusion is consistent with the lack of ClinVar reporting rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.429200	Structured	0.724779	Binding	0.302	0.891	0.250							-8.288	Likely Pathogenic	0.727	Likely Pathogenic	Likely Benign	0.155	Likely Benign	0.1339	0.4356											-4.42	Deleterious	0.998	Probably Damaging	0.840	Possibly Damaging	3.88	Benign	0.00	Affected			-3	-3	2.9	46.09
c.2804C>T	A935V 2D AIThe SynGAP1 missense variant A935V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also leans benign (2 benign vs. 1 pathogenic votes). Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for A935V, and this conclusion does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.736850	Disordered	0.980490	Binding	0.286	0.865	0.625							-4.750	Likely Benign	0.397	Ambiguous	Likely Benign	0.194	Likely Benign	0.1340	0.5941											-2.06	Neutral	0.999	Probably Damaging	0.996	Probably Damaging	2.30	Pathogenic	0.00	Affected			0	0	2.4	28.05
c.3178G>T	G1060C 2D AIThe SynGAP1 missense variant G1060C is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for G1060C, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.979242	Disordered	0.913048	Binding	0.407	0.928	0.875							-9.630	Likely Pathogenic	0.116	Likely Benign	Likely Benign	0.363	Likely Benign	0.1340	0.4227											-0.60	Neutral	0.999	Probably Damaging	0.917	Probably Damaging	2.63	Benign	0.12	Tolerated			-3	-3	2.9	46.09
c.1387G>C	D463H 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant D463H is not reported in ClinVar and is absent from gnomAD. Consensus from standard prediction algorithms shows a split: benign predictions come from REVEL, FoldX, SIFT, and FATHMM, whereas pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts Pathogenic, SGM Consensus confirms Likely Pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, remains Uncertain. No evidence from ClinVar contradicts these findings. Overall, the preponderance of computational evidence indicates that D463H is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.260850	Structured	0.305622	Uncertain	0.940	0.176	0.000							-13.151	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	0.356	Likely Benign	0.1341	0.6156		0.20	Likely Benign	0.1	0.85	Ambiguous	0.53	Ambiguous	0.57	Ambiguous	-5.96	Deleterious	0.996	Probably Damaging	0.852	Possibly Damaging	3.35	Benign	0.11	Tolerated			1	-1	0.3	22.05
c.2199G>C	Q733H 2D AIThe SynGAP1 missense variant Q733H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; the Foldetta stability analysis is not available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.874069	Disordered	0.410831	Uncertain	0.331	0.686	0.875							-5.741	Likely Benign	0.207	Likely Benign	Likely Benign	0.140	Likely Benign	0.1341	0.2263											-2.47	Neutral	0.990	Probably Damaging	0.780	Possibly Damaging	2.52	Benign	0.02	Affected			3	0	0.3	9.01
c.2199G>T	Q733H 2D AIThe SynGAP1 missense variant Q733H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. No Foldetta stability result is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect for Q733H, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.874069	Disordered	0.410831	Uncertain	0.331	0.686	0.875							-5.741	Likely Benign	0.207	Likely Benign	Likely Benign	0.140	Likely Benign	0.1341	0.2263											-2.47	Neutral	0.990	Probably Damaging	0.780	Possibly Damaging	2.52	Benign	0.02	Affected			3	0	0.3	9.01
c.3603G>C	E1201D 2D AIThe SynGAP1 missense variant E1201D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, PROVEAN, and SIFT, whereas pathogenic calls are made by polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy consensus methods reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely pathogenic classification. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Overall, the preponderance of evidence points to a pathogenic effect, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.525368	Disordered	0.481868	Uncertain	0.870	0.596	0.250							-8.727	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	0.150	Likely Benign	0.1341	0.3335											-1.55	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	1.66	Pathogenic	0.51	Tolerated			3	2	0.0	-14.03
c.3603G>T	E1201D 2D AIThe SynGAP1 missense variant E1201D is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, PROVEAN, and SIFT, whereas pathogenic calls are made by polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy consensus methods reinforce the pathogenic signal: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely pathogenic classification. Foldetta, a protein‑folding stability predictor, has no available result for this residue. Overall, the preponderance of evidence points to a pathogenic effect, and this assessment does not contradict any ClinVar annotation because no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.525368	Disordered	0.481868	Uncertain	0.870	0.596	0.250							-8.727	Likely Pathogenic	0.965	Likely Pathogenic	Likely Pathogenic	0.150	Likely Benign	0.1341	0.3335											-1.55	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	1.66	Pathogenic	0.51	Tolerated			3	2	0.0	-14.03
c.180T>A	D60E 2D AIThe SynGAP1 D60E missense variant has no ClinVar record and is not listed in gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also resolves to benign. Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.284882	Structured	0.480942	Uncertain	0.521	0.676	0.000							-3.818	Likely Benign	0.780	Likely Pathogenic	Likely Benign	0.089	Likely Benign	0.1342	0.7869											-0.90	Neutral	0.643	Possibly Damaging	0.785	Possibly Damaging	4.05	Benign	0.00	Affected			3	2	0.0	14.03
c.180T>G	D60E 2D AIThe SynGAP1 D60E missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also resolves to benign. Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.284882	Structured	0.480942	Uncertain	0.521	0.676	0.000							-3.818	Likely Benign	0.780	Likely Pathogenic	Likely Benign	0.089	Likely Benign	0.1342	0.7869											-0.90	Neutral	0.643	Possibly Damaging	0.785	Possibly Damaging	4.05	Benign	0.00	Affected			3	2	0.0	14.03
c.2243T>G	L748R 2D AIThe SynGAP1 missense variant L748R is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33441708‑T‑G). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, SGM‑Consensus is likely benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict the current ClinVar “Uncertain” designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.703578	Disordered	0.611637	Binding	0.339	0.863	0.750	Conflicting		2	6-33441708-T-G	3	1.86e-6	-3.331	Likely Benign	0.245	Likely Benign	Likely Benign	0.055	Likely Benign	0.1342	0.0888											-0.67	Neutral	0.912	Possibly Damaging	0.448	Possibly Damaging	2.73	Benign	0.02	Affected	4.32	2	-3	-2	-8.3	43.03
c.3074A>G	Q1025R 2D AIThe SynGAP1 missense variant Q1025R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (both HumDiv and HumVar) predict a pathogenic outcome. AlphaMissense‑Default remains uncertain, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of computational evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.879233	Disordered	0.993410	Binding	0.363	0.746	0.500							-4.435	Likely Benign	0.480	Ambiguous	Likely Benign	0.101	Likely Benign	0.1342	0.2656											-1.28	Neutral	0.818	Possibly Damaging	0.453	Possibly Damaging	2.72	Benign	0.10	Tolerated			1	1	-1.0	28.06
c.3416A>G	Q1139R 2D AIThe SynGAP1 missense variant Q1139R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign effect, and this is consistent with the lack of ClinVar annotation—there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.908098	Disordered	0.721191	Binding	0.313	0.866	1.000							-4.249	Likely Benign	0.267	Likely Benign	Likely Benign	0.315	Likely Benign	0.1342	0.2405											-1.91	Neutral	0.126	Benign	0.138	Benign	5.47	Benign	0.00	Affected			1	1	-1.0	28.06
c.706G>A	A236T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 A236T missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Those that predict a pathogenic impact are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. Predictions that are uncertain or inconclusive are FoldX, Rosetta, Foldetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is a 2‑vs‑2 tie and thus unavailable. Foldetta, which integrates FoldX‑MD and Rosetta outputs, is also uncertain. Overall, six tools favor pathogenicity versus three favor benign, and no high‑confidence consensus tool contradicts this trend. Therefore, the variant is most likely pathogenic, and this assessment does not conflict with any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.185198	Structured	0.329926	Uncertain	0.775	0.330	0.000							-8.319	Likely Pathogenic	0.240	Likely Benign	Likely Benign	0.811	Likely Pathogenic	0.1342	0.6926		0.73	Ambiguous	0.2	1.58	Ambiguous	1.16	Ambiguous	0.83	Ambiguous	-3.35	Deleterious	0.982	Probably Damaging	0.747	Possibly Damaging	5.79	Benign	0.03	Affected			1	0	-2.5	30.03
c.1132G>C	G378R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant G378R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from premPS, PROVEAN, and SIFT, while pathogenic predictions arise from REVEL, FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts benign, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—classifies the variant as pathogenic, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also indicates pathogenicity. Overall, the preponderance of evidence points to a pathogenic impact for G378R. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.767246	Disordered	0.432858	Uncertain	0.341	0.915	0.625							-8.863	Likely Pathogenic	0.745	Likely Pathogenic	Likely Benign	0.653	Likely Pathogenic	0.1343	0.4356		12.27	Destabilizing	6.3	13.17	Destabilizing	12.72	Destabilizing	0.12	Likely Benign	-0.96	Neutral	1.000	Probably Damaging	0.996	Probably Damaging	1.32	Pathogenic	0.06	Tolerated			-3	-2	-4.1	99.14
c.3218C>G	S1073C 2D AISynGAP1 missense variant S1073C is recorded in gnomAD (ID 6‑33443770‑C‑G) but has no ClinVar submission. Functional prediction tools show mixed results: benign calls come from REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls are made by polyPhen‑2 (HumDiv and HumVar), SIFT, and ESM1b. The AlphaMissense‑Default score is uncertain. A consensus from the SGM framework (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive because the votes are split. High‑accuracy methods give a benign prediction from AlphaMissense‑Optimized; the SGM Consensus remains ambiguous, and Foldetta stability analysis is unavailable. Consequently, the evidence does not strongly favor either outcome. The variant is most likely of uncertain significance, with no contradiction to ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.916840	Disordered	0.985818	Binding	0.313	0.905	0.750				6-33443770-C-G	1	6.23e-7	-8.862	Likely Pathogenic	0.461	Ambiguous	Likely Benign	0.137	Likely Benign	0.1343	0.6088											-1.52	Neutral	0.997	Probably Damaging	0.840	Possibly Damaging	3.81	Benign	0.00	Affected	3.77	5	-1	0	3.3	16.06
c.3256C>A	P1086T 2D AIThe SynGAP1 missense variant P1086T is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33443808‑C‑A). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign). Foldetta results are unavailable. Overall, the majority of predictions (five pathogenic vs. four benign) lean toward a pathogenic impact. The variant is most likely pathogenic based on the available computational evidence, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.849326	Disordered	0.977190	Binding	0.393	0.885	1.000				6-33443808-C-A			-4.181	Likely Benign	0.568	Likely Pathogenic	Likely Benign	0.229	Likely Benign	0.1343	0.5848											-2.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.75	Benign	0.00	Affected	3.77	5	-1	0	0.9	3.99
c.3364G>T	G1122C 2D AIThe SynGAP1 missense variant G1122C is listed in ClinVar with no submitted interpretation and is present in gnomAD (variant ID 6‑33443916‑G‑T). Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote). In contrast, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; Foldetta results are not available. Overall, the majority of evidence—including the high‑confidence tools—supports a benign classification, and this conclusion does not contradict the ClinVar status, which currently has no pathogenic designation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.896620	Disordered	0.814918	Binding	0.357	0.932	0.875				6-33443916-G-T			-8.895	Likely Pathogenic	0.110	Likely Benign	Likely Benign	0.375	Likely Benign	0.1343	0.4227											-1.30	Neutral	0.975	Probably Damaging	0.733	Possibly Damaging	4.48	Benign	0.08	Tolerated	3.77	5	-3	-3	2.9	46.09
c.517C>G	L173V 2D AIThe SynGAP1 missense variant L173V is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Only ESM1b predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized is benign, and the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign majority vote. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.534167	Disordered	0.491566	Uncertain	0.390	0.631	0.375							-8.320	Likely Pathogenic	0.495	Ambiguous	Likely Benign	0.100	Likely Benign	0.1343	0.3217											-0.95	Neutral	0.131	Benign	0.058	Benign	4.05	Benign	0.22	Tolerated			2	1	0.4	-14.03
c.1525G>A	A509T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A509T is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are ESM1b and FATHMM. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive (2 benign vs 2 pathogenic). Foldetta, which integrates FoldX‑MD and Rosetta outputs, is uncertain and therefore unavailable for interpretation. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.025762	Structured	0.250110	Uncertain	0.923	0.256	0.000							-8.961	Likely Pathogenic	0.171	Likely Benign	Likely Benign	0.360	Likely Benign	0.1344	0.5593		0.95	Ambiguous	0.4	0.61	Ambiguous	0.78	Ambiguous	0.04	Likely Benign	-2.15	Neutral	0.031	Benign	0.058	Benign	-1.25	Pathogenic	0.32	Tolerated			1	0	-2.5	30.03
c.1682T>A	F561Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F561Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a deleterious effect include REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). No tool predicts a benign outcome; the remaining predictions (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) are uncertain or unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Based on the consensus of the majority of evidence‑based predictors, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024826	Structured	0.018013	Uncertain	0.903	0.196	0.000							-12.692	Likely Pathogenic	0.950	Likely Pathogenic	Ambiguous	0.693	Likely Pathogenic	0.1344	0.1120		1.54	Ambiguous	0.1	0.75	Ambiguous	1.15	Ambiguous	1.28	Destabilizing	-2.99	Deleterious	0.988	Probably Damaging	0.976	Probably Damaging	-1.34	Pathogenic	0.01	Affected			7	3	-4.1	16.00
c.1784T>G	L595R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L595R is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include only FATHMM, while the majority of tools (SGM‑Consensus, REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact; FoldX and Foldetta are uncertain. High‑accuracy methods give a pathogenic signal: AlphaMissense‑Optimized is pathogenic, SGM‑Consensus is likely pathogenic, and Foldetta remains uncertain. Overall, the evidence strongly favors a pathogenic effect, and this conclusion does not contradict any ClinVar annotation, as no ClinVar record exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.015344	Structured	0.128444	Uncertain	0.920	0.150	0.000							-14.601	Likely Pathogenic	0.989	Likely Pathogenic	Likely Pathogenic	0.707	Likely Pathogenic	0.1344	0.1005		1.22	Ambiguous	0.0	2.20	Destabilizing	1.71	Ambiguous	1.52	Destabilizing	-5.97	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.76	Benign	0.00	Affected			-3	-2	-8.3	43.03
c.181G>C	E61Q 2D AIThe SynGAP1 missense variant E61Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability result is available. Overall, the majority of evidence points to a benign effect for E61Q, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.352862	Structured	0.477329	Uncertain	0.518	0.699	0.125							-5.443	Likely Benign	0.267	Likely Benign	Likely Benign	0.058	Likely Benign	0.1344	0.5617											-0.41	Neutral	0.659	Possibly Damaging	0.775	Possibly Damaging	4.18	Benign	0.00	Affected			2	2	0.0	-0.98
c.2050G>C	D684H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D684H is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that agree on a benign effect include only FATHMM; all other evaluated algorithms (REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact, and the SGM‑Consensus score is “Likely Pathogenic.” High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions are inconclusive or missing. Based on the overwhelming majority of pathogenic predictions, the variant is most likely pathogenic, which does not contradict the current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.254060	Structured	0.153798	Uncertain	0.870	0.282	0.000	Uncertain		1				-14.194	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.613	Likely Pathogenic	0.1344	0.6618		3.36	Destabilizing	1.0	2.95	Destabilizing	3.16	Destabilizing	0.55	Ambiguous	-6.98	Deleterious	1.000	Probably Damaging	0.972	Probably Damaging	3.36	Benign	0.00	Affected	3.42	17	-1	1	0.3	22.05
c.2258C>T	A753V 2D AIThe SynGAP1 missense variant A753V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the variant as benign. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign. Foldetta results are not available, so they do not influence the assessment. Overall, the majority of computational evidence indicates that A753V is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.521092	Disordered	0.722781	Binding	0.381	0.873	0.625							-3.759	Likely Benign	0.097	Likely Benign	Likely Benign	0.083	Likely Benign	0.1344	0.5953											-1.55	Neutral	0.669	Possibly Damaging	0.192	Benign	2.71	Benign	0.18	Tolerated			0	0	2.4	28.05
c.77G>T	G26V 2D AIThe SynGAP1 missense variant G26V is reported in gnomAD (variant ID 6‑33423486‑G‑T) but has no ClinVar entry. Functional prediction tools cluster into two groups: the benign‑predicted set includes REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; the pathogenic‑predicted set contains polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. The high‑accuracy consensus methods reinforce the benign assessment: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Benign.” No Foldetta stability result is available, so it does not influence the conclusion. Overall, the majority of evidence points to a benign effect for G26V, and this is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.486429	Structured	0.438291	Uncertain	0.351	0.878	0.375				6-33423486-G-T	1	6.20e-7	-3.499	Likely Benign	0.165	Likely Benign	Likely Benign	0.197	Likely Benign	0.1344	0.4333											-2.34	Neutral	0.994	Probably Damaging	0.990	Probably Damaging	3.89	Benign	0.00	Affected	4.32	1	-3	-1	4.6	42.08
c.1634T>G	M545R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M545R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that classify the variant as benign include SIFT, FoldX, and Foldetta, whereas the majority of tools predict it to be pathogenic: SGM‑Consensus, REVEL, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Rosetta’s assessment is uncertain. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts pathogenicity; the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts benign. Overall, the preponderance of evidence from both general and high‑accuracy predictors points to a pathogenic effect. This conclusion does not contradict ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.025762	Structured	0.012875	Uncertain	0.955	0.311	0.000							-9.223	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.773	Likely Pathogenic	0.1345	0.0837		-0.27	Likely Benign	0.1	0.95	Ambiguous	0.34	Likely Benign	1.07	Destabilizing	-4.76	Deleterious	0.987	Probably Damaging	0.971	Probably Damaging	-1.23	Pathogenic	0.36	Tolerated			0	-1	-6.4	24.99
c.1708G>A	A570T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A570T is not reported in ClinVar and is absent from gnomAD. Prediction tools that provide a definitive call all indicate a deleterious effect: SGM‑Consensus (Likely Pathogenic), REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default all predict pathogenicity. No tool reports a benign outcome; the remaining predictions (FoldX, Rosetta, Foldetta, premPS, AlphaMissense‑Optimized) are uncertain and therefore do not influence the overall assessment. High‑accuracy methods specifically show SGM‑Consensus as Likely Pathogenic, AlphaMissense‑Optimized as uncertain, and Foldetta as uncertain. Taken together, the majority of conclusive predictions support a pathogenic effect. Consequently, the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.046336	Structured	0.054494	Uncertain	0.932	0.263	0.000							-11.390	Likely Pathogenic	0.801	Likely Pathogenic	Ambiguous	0.568	Likely Pathogenic	0.1345	0.3874		1.45	Ambiguous	0.3	1.67	Ambiguous	1.56	Ambiguous	0.86	Ambiguous	-3.28	Deleterious	0.998	Probably Damaging	0.993	Probably Damaging	-1.26	Pathogenic	0.05	Affected			1	0	-2.5	30.03
c.1807A>C	M603L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 M603L missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that classify the variant as benign include FoldX, premPS, PROVEAN, SIFT, AlphaMissense‑Optimized, and the protein‑folding stability method Foldetta. Those that predict pathogenicity are REVEL, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. Two tools give uncertain results: Rosetta and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, more evidence supports a benign effect (six benign versus five pathogenic predictions, with two uncertain). Thus, the variant is most likely benign, and this assessment does not contradict any ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.011342	Structured	0.197847	Uncertain	0.942	0.176	0.000							-7.134	In-Between	0.590	Likely Pathogenic	Likely Benign	0.548	Likely Pathogenic	0.1345	0.3227		0.04	Likely Benign	0.1	0.86	Ambiguous	0.45	Likely Benign	-0.18	Likely Benign	-2.16	Neutral	0.484	Possibly Damaging	0.654	Possibly Damaging	-0.98	Pathogenic	0.52	Tolerated			4	2	1.9	-18.03
c.1807A>T	M603L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 M603L missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include FoldX, Foldetta, premPS, PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Default. Rosetta and ESM1b give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools lean toward a benign interpretation, but the SGM Consensus indicates pathogenicity, leaving the variant’s clinical significance uncertain. This assessment does not contradict any ClinVar status, as no ClinVar entry exists for M603L. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.011342	Structured	0.197847	Uncertain	0.942	0.176	0.000							-7.134	In-Between	0.590	Likely Pathogenic	Likely Benign	0.548	Likely Pathogenic	0.1345	0.3227		0.04	Likely Benign	0.1	0.86	Ambiguous	0.45	Likely Benign	-0.18	Likely Benign	-2.16	Neutral	0.484	Possibly Damaging	0.654	Possibly Damaging	-0.98	Pathogenic	0.52	Tolerated			4	2	1.9	-18.03
c.2132T>G	L711R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L711R lies in the GAP domain. ClinVar has no entry for this variant, and it is not present in gnomAD. Prediction tools that agree on a benign effect are REVEL and FATHMM; all other evaluated algorithms (FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) predict a pathogenic impact, and the SGM‑Consensus score is “Likely Pathogenic.” High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. No predictions or stability results are missing or inconclusive. Based on the overwhelming majority of computational evidence, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.308712	Structured	0.377436	Uncertain	0.950	0.364	0.000							-14.009	Likely Pathogenic	0.994	Likely Pathogenic	Likely Pathogenic	0.432	Likely Benign	0.1345	0.0488		3.71	Destabilizing	0.0	3.98	Destabilizing	3.85	Destabilizing	2.13	Destabilizing	-5.71	Deleterious	0.999	Probably Damaging	0.992	Probably Damaging	3.35	Benign	0.00	Affected			-3	-2	-8.3	43.03
c.2405G>T	G802V 2D AIThe SynGAP1 missense variant G802V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the only pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign. No Foldetta stability analysis is available for this variant. Overall, the consensus of the available predictions indicates that G802V is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.894241	Disordered	0.681966	Binding	0.294	0.898	0.625							-3.871	Likely Benign	0.126	Likely Benign	Likely Benign	0.078	Likely Benign	0.1345	0.3533											-1.49	Neutral	0.411	Benign	0.321	Benign	2.67	Benign	0.00	Affected			-1	-3	4.6	42.08
c.2576G>C	S859T 2D AIThe SynGAP1 missense variant S859T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. ESM1b is uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.648219	Disordered	0.497075	Uncertain	0.288	0.819	0.375							-7.155	In-Between	0.089	Likely Benign	Likely Benign	0.154	Likely Benign	0.1345	0.6434											-0.97	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	4.02	Benign	0.24	Tolerated			1	1	0.1	14.03
c.3038C>G	S1013C 2D AIThe SynGAP1 missense variant S1013C is listed in ClinVar with an uncertain significance (ClinVar ID 934570.0) and is present in gnomAD (ID 6‑33443590‑C‑G). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion does not contradict the ClinVar status, which remains uncertain. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.823549	Disordered	0.899570	Binding	0.308	0.846	0.625	Uncertain		1	6-33443590-C-G	4	2.48e-6	-6.745	Likely Benign	0.110	Likely Benign	Likely Benign	0.058	Likely Benign	0.1345	0.5817											-2.06	Neutral	0.898	Possibly Damaging	0.579	Possibly Damaging	2.64	Benign	0.05	Affected	3.77	5	0	-1	3.3	16.06
c.3079A>C	N1027H 2D AIThe SynGAP1 missense variant N1027H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. In contrast, polyPhen‑2 (HumDiv and HumVar) predict pathogenic. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of predictions, including the high‑accuracy tools, indicate that the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.831250	Disordered	0.994357	Binding	0.347	0.745	0.500							-4.185	Likely Benign	0.193	Likely Benign	Likely Benign	0.074	Likely Benign	0.1345	0.7176											-1.44	Neutral	0.970	Probably Damaging	0.799	Possibly Damaging	2.74	Benign	0.07	Tolerated			2	1	0.3	23.04
c.3712C>A	Q1238K 2D AIThe SynGAP1 missense variant Q1238K is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also yields a benign prediction. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact. This conclusion is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.562014	Disordered	0.548882	Binding	0.855	0.545	0.250							-8.631	Likely Pathogenic	0.513	Ambiguous	Likely Benign	0.195	Likely Benign	0.1345	0.3494											-1.70	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	2.51	Benign	0.30	Tolerated			1	1	-0.4	0.04
c.3885G>C	Q1295H 2D AIThe SynGAP1 missense variant Q1295H is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show discordant results: benign calls come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further highlight this split: AlphaMissense‑Optimized predicts a benign effect, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely pathogenic outcome. No Foldetta stability analysis is available for this residue. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion does not contradict any existing ClinVar annotation, as none is present. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.852992	Disordered	0.892719	Binding	0.499	0.801	0.625							-4.851	Likely Benign	0.588	Likely Pathogenic	Likely Benign	0.349	Likely Benign	0.1345	0.3203											-4.08	Deleterious	0.991	Probably Damaging	0.986	Probably Damaging	2.24	Pathogenic	0.00	Affected			3	0	0.3	9.01
c.3885G>T	Q1295H 2D AIThe SynGAP1 missense variant Q1295H is catalogued in gnomAD (ID 6‑33447933‑G‑T) but has no ClinVar submission. Functional prediction tools show a split: benign calls come from REVEL, ESM1b, and AlphaMissense‑Optimized, whereas pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. When predictions are grouped, 3 tools predict benign and 6 predict pathogenic. High‑accuracy assessments further clarify the picture: AlphaMissense‑Optimized remains benign, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—labels the variant as Likely Pathogenic. Foldetta, a protein‑folding stability method that integrates FoldX‑MD and Rosetta outputs, has no available result for this substitution. Overall, the preponderance of evidence points to a pathogenic effect, and this assessment does not conflict with ClinVar, which currently contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.852992	Disordered	0.892719	Binding	0.499	0.801	0.625				6-33447933-G-T			-4.851	Likely Benign	0.588	Likely Pathogenic	Likely Benign	0.349	Likely Benign	0.1345	0.3203											-4.08	Deleterious	0.991	Probably Damaging	0.986	Probably Damaging	2.24	Pathogenic	0.00	Affected			3	0	0.3	9.01
c.3949G>T	G1317C 2D AIThe SynGAP1 missense variant G1317C is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33451823‑G‑T). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also predicts benign, while Foldetta results are unavailable. Overall, the majority of reliable predictions favor a benign impact, and this is consistent with the lack of ClinVar evidence. Thus, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.908098	Disordered	0.971158	Binding	0.385	0.879	0.750				6-33451823-G-T			-5.850	Likely Benign	0.342	Ambiguous	Likely Benign	0.162	Likely Benign	0.1345	0.3753											-3.83	Deleterious	0.939	Possibly Damaging	0.570	Possibly Damaging	3.99	Benign	0.00	Affected	3.77	5	-3	-3	2.9	46.09
c.1261G>A	A421T 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A421T is not reported in ClinVar and is present in gnomAD (ID 6‑33438166‑G‑A). Functional prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; the SGM‑Consensus score is “Likely Pathogenic.” Uncertain results from FoldX and premPS are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, the SGM‑Consensus as likely pathogenic, and Foldetta as benign. Overall, the majority of consensus predictions lean toward a benign impact, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.067594	Structured	0.404927	Uncertain	0.965	0.257	0.000				6-33438166-G-A	1	6.19e-7	-9.217	Likely Pathogenic	0.975	Likely Pathogenic	Likely Pathogenic	0.179	Likely Benign	0.1346	0.4439		0.75	Ambiguous	0.2	0.18	Likely Benign	0.47	Likely Benign	0.99	Ambiguous	-3.12	Deleterious	0.353	Benign	0.136	Benign	3.43	Benign	0.09	Tolerated	3.37	29	0	1	-2.5	30.03
c.1802C>A	A601E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A601E is listed in ClinVar with an “Uncertain” status and is not reported in gnomAD. Prediction tools that assess pathogenicity largely agree: REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic effect, while only FATHMM predicts a benign outcome. High‑accuracy assessments reinforce this consensus: AlphaMissense‑Optimized indicates pathogenicity; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports “Likely Pathogenic”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. No predictions or stability results are missing or inconclusive. Based on the overwhelming agreement among these tools, the variant is most likely pathogenic, which does not contradict its current ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.008895	Structured	0.174517	Uncertain	0.955	0.156	0.000	Conflicting		2				-16.752	Likely Pathogenic	0.992	Likely Pathogenic	Likely Pathogenic	0.588	Likely Pathogenic	0.1346	0.1444		6.68	Destabilizing	0.8	5.76	Destabilizing	6.22	Destabilizing	1.24	Destabilizing	-4.98	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.54	Benign	0.00	Affected	3.37	35	0	-1	-5.3	58.04	240.0	-82.3	0.0	0.0	0.7	0.1		X	X				X	Potentially Pathogenic	The methyl side chain of Ala601, located on an α helix (res. Glu582-Met603), packs hydrophobically against other hydrophobic residues in the inter-helix space (e.g., Phe597, Leu598, Leu506, Phe608).In the variant simulations, the carboxylate group of Glu601 faces the inter-helix space and is forced to shift slightly away from the hydrophobic niche. Additionally, in two of the simulations, Glu601 forms a salt bridge with Arg499, causing the otherwise stable salt bridge between Arg499 and Glu496 at the outer surface of an α helix (res. Leu489-Glu519) to break due to the residue swap.These effects suggest that the protein folding process could be seriously affected. Moreover, due to its location at the GAP-Ras interface, it could also impact the complex formation with the GTPase.
c.2104C>A	Q702K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q702K is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign and Foldetta as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, the majority of evidence supports a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.074921	Structured	0.397258	Uncertain	0.907	0.345	0.000							-8.750	Likely Pathogenic	0.338	Likely Benign	Likely Benign	0.224	Likely Benign	0.1346	0.2524		-0.23	Likely Benign	0.0	0.26	Likely Benign	0.02	Likely Benign	0.08	Likely Benign	-2.86	Deleterious	0.863	Possibly Damaging	0.773	Possibly Damaging	3.46	Benign	0.08	Tolerated			1	1	-0.4	0.04
c.3361A>C	S1121R 2D AIThe SynGAP1 missense variant S1121R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign, reflecting the majority of benign predictions. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact for S1121R, and this conclusion is consistent with the lack of ClinVar reporting. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.894241	Disordered	0.810024	Binding	0.365	0.935	0.875							-6.945	Likely Benign	0.597	Likely Pathogenic	Likely Benign	0.142	Likely Benign	0.1346	0.3431											-0.34	Neutral	0.016	Benign	0.015	Benign	5.45	Benign	0.00	Affected	3.77	5	-1	0	-3.7	69.11
c.3363C>A	S1121R 2D AIThe SynGAP1 missense variant S1121R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Benign, and Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.894241	Disordered	0.810024	Binding	0.365	0.935	0.875							-6.945	Likely Benign	0.597	Likely Pathogenic	Likely Benign	0.100	Likely Benign	0.1346	0.3431											-0.34	Neutral	0.016	Benign	0.015	Benign	5.45	Benign	0.00	Affected	3.77	5	-1	0	-3.7	69.11
c.3363C>G	S1121R 2D AIThe SynGAP1 missense variant S1121R is catalogued in gnomAD (ID 6‑33443915‑C‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Optimized all report benign. Only SIFT and AlphaMissense‑Default predict pathogenicity, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.894241	Disordered	0.810024	Binding	0.365	0.935	0.875				6-33443915-C-G			-6.945	Likely Benign	0.597	Likely Pathogenic	Likely Benign	0.101	Likely Benign	0.1346	0.3431											-0.34	Neutral	0.016	Benign	0.015	Benign	5.45	Benign	0.00	Affected	3.77	5	-1	0	-3.7	69.11
c.3988C>G	Q1330E 2D AIThe SynGAP1 missense variant Q1330E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign and the SGM‑Consensus also reports likely benign; Foldetta results are unavailable. Overall, the consensus of the available predictions points to a benign impact, and this is consistent with the lack of ClinVar evidence, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.943310	Disordered	0.931969	Binding	0.369	0.752	0.875							-3.428	Likely Benign	0.281	Likely Benign	Likely Benign	0.035	Likely Benign	0.1346	0.2409											-1.12	Neutral	0.613	Possibly Damaging	0.240	Benign	3.98	Benign	0.06	Tolerated			2	2	0.0	0.98
c.451G>A	D151N 2D AIThe SynGAP1 missense variant D151N has no ClinVar entry (ClinVar status: not reported) and is absent from gnomAD (gnomAD ID: none). Prediction tools that classify the variant as benign include REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—predict it to be pathogenic. The SGM‑Consensus result (Likely Pathogenic) is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence from multiple in silico predictors indicates that D151N is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is currently assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.529623	Disordered	0.503277	Binding	0.342	0.841	0.625							-8.479	Likely Pathogenic	0.970	Likely Pathogenic	Likely Pathogenic	0.185	Likely Benign	0.1346	0.8186											-2.51	Deleterious	0.993	Probably Damaging	0.984	Probably Damaging	3.90	Benign	0.01	Affected			2	1	0.0	-0.98
c.1220A>G	Q407R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q407R has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, SIFT, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and AlphaMissense‑Default; premPS is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. With two of the three high‑accuracy methods indicating benign and the remaining one pathogenic, the overall evidence leans toward a benign classification. This conclusion does not contradict ClinVar status, which is currently unreported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.109221	Structured	0.382522	Uncertain	0.916	0.271	0.000							-13.263	Likely Pathogenic	0.693	Likely Pathogenic	Likely Benign	0.340	Likely Benign	0.1347	0.1596		0.15	Likely Benign	0.2	0.09	Likely Benign	0.12	Likely Benign	0.65	Ambiguous	-3.52	Deleterious	0.909	Possibly Damaging	0.889	Possibly Damaging	4.02	Benign	0.17	Tolerated			1	1	-1.0	28.06
c.1610C>A	A537E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A537E is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, premPS, PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. No prediction or stability result is missing or inconclusive. Based on the overall consensus of the available tools, the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.116183	Structured	0.037313	Uncertain	0.928	0.362	0.000							-5.120	Likely Benign	0.450	Ambiguous	Likely Benign	0.378	Likely Benign	0.1347	0.1566		-0.14	Likely Benign	0.1	0.00	Likely Benign	-0.07	Likely Benign	0.23	Likely Benign	-1.78	Neutral	0.987	Probably Damaging	0.838	Possibly Damaging	-1.04	Pathogenic	1.00	Tolerated			0	-1	-5.3	58.04
c.3349G>T	G1117C 2D AIThe SynGAP1 missense variant G1117C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is not contradicted by ClinVar status, as no ClinVar classification exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.882776	Disordered	0.853192	Binding	0.323	0.914	0.750							-9.045	Likely Pathogenic	0.112	Likely Benign	Likely Benign	0.359	Likely Benign	0.1347	0.4612											-1.30	Neutral	0.994	Probably Damaging	0.840	Possibly Damaging	4.56	Benign	0.03	Affected			-3	-3	2.9	46.09
c.3685C>A	Q1229K 2D AISynGAP1 missense variant Q1229K is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign calls from REVEL, PROVEAN, SIFT, and AlphaMissense‑Optimized; pathogenic calls from polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. AlphaMissense‑Default remains uncertain. High‑accuracy assessment shows AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic; Foldetta stability analysis is unavailable. Overall, the evidence is split, with an equal number of benign and pathogenic predictions, and the high‑accuracy tools provide one benign and one pathogenic call. Thus, the variant is most likely pathogenic based on the preponderance of pathogenic predictions, and this assessment does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.490133	Structured	0.466729	Uncertain	0.865	0.544	0.375							-9.803	Likely Pathogenic	0.471	Ambiguous	Likely Benign	0.159	Likely Benign	0.1347	0.2883											-2.36	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	1.82	Pathogenic	0.22	Tolerated			1	1	-0.4	0.04
c.2018T>G	L673R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L673R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls come from REVEL, polyPhen‑2 HumVar, FATHMM, and AlphaMissense‑Optimized; pathogenic calls come from Rosetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and the SGM Consensus (majority vote). FoldX and Foldetta are inconclusive. High‑accuracy assessments give a benign result from AlphaMissense‑Optimized, a likely pathogenic verdict from the SGM Consensus, and an uncertain outcome from Foldetta. Overall, the majority of evidence points toward pathogenicity, and this conclusion does not conflict with the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.060549	Structured	0.104692	Uncertain	0.545	0.369	0.000							-14.474	Likely Pathogenic	0.714	Likely Pathogenic	Likely Benign	0.178	Likely Benign	0.1348	0.1015		1.10	Ambiguous	0.2	2.04	Destabilizing	1.57	Ambiguous	1.23	Destabilizing	-3.81	Deleterious	0.991	Probably Damaging	0.433	Benign	3.36	Benign	0.03	Affected			-3	-2	-8.3	43.03
c.3367G>T	G1123C 2D AIThe SynGAP1 missense variant G1123C is listed in gnomAD (ID 6‑33443919‑G‑T) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 (HumDiv and HumVar) and ESM1b predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus also as likely benign; Foldetta results are unavailable. Overall, the majority of evidence—including the consensus and high‑accuracy tools—supports a benign classification. This conclusion is not contradicted by ClinVar, which contains no record for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.837511	Disordered	0.827246	Binding	0.346	0.934	0.875				6-33443919-G-T	1	6.64e-7	-9.329	Likely Pathogenic	0.118	Likely Benign	Likely Benign	0.353	Likely Benign	0.1348	0.4227											-1.17	Neutral	0.994	Probably Damaging	0.840	Possibly Damaging	4.34	Benign	0.10	Tolerated	3.77	5	-3	-3	2.9	46.09
c.3982C>T	R1328W 2D AIThe SynGAP1 missense variant R1328W is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33451856‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, and AlphaMissense‑Optimized, whereas polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default predict a pathogenic outcome. ESM1b is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also resolves to benign, while Foldetta results are unavailable. Taken together, the majority of high‑confidence predictions favor a benign impact, and there is no conflict with ClinVar status. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.887230	Disordered	0.911775	Binding	0.360	0.762	0.875				6-33451856-C-T	4	2.56e-6	-7.022	In-Between	0.779	Likely Pathogenic	Likely Benign	0.125	Likely Benign	0.1349	0.2906											-2.40	Neutral	0.997	Probably Damaging	0.756	Possibly Damaging	4.04	Benign	0.00	Affected	3.77	5	-3	2	3.6	30.03
c.3989A>G	Q1330R 2D AIThe SynGAP1 missense variant Q1330R is listed in gnomAD (ID 6‑33451863‑A‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.943310	Disordered	0.931969	Binding	0.369	0.752	0.875				6-33451863-A-G			-3.601	Likely Benign	0.472	Ambiguous	Likely Benign	0.031	Likely Benign	0.1349	0.2333											-1.65	Neutral	0.898	Possibly Damaging	0.341	Benign	3.95	Benign	0.03	Affected	3.77	5	1	1	-1.0	28.06
c.2042G>T	G681V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G681V is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, whereas the majority of algorithms—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Default—classify the change as pathogenic. High‑accuracy methods give the following results: AlphaMissense‑Optimized is uncertain; SGM‑Consensus predicts a likely pathogenic effect; Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, reports a pathogenic outcome. No other high‑confidence predictions are available. Taken together, the consensus of pathogenic predictions outweighs the single benign call, indicating that G681V is most likely pathogenic. This assessment is not contradicted by ClinVar, which contains no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.301917	Structured	0.140647	Uncertain	0.694	0.320	0.000							-14.043	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous	0.572	Likely Pathogenic	0.1350	0.3840		3.21	Destabilizing	2.0	6.12	Destabilizing	4.67	Destabilizing	0.64	Ambiguous	-8.98	Deleterious	0.999	Probably Damaging	0.928	Probably Damaging	3.33	Benign	0.01	Affected			-1	-3	4.6	42.08
c.3095T>G	L1032R 2D AIThe SynGAP1 missense variant L1032R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.865454	Disordered	0.995318	Binding	0.365	0.735	0.500							-2.658	Likely Benign	0.707	Likely Pathogenic	Likely Benign	0.099	Likely Benign	0.1350	0.1919											-1.03	Neutral	0.995	Probably Damaging	0.892	Possibly Damaging	2.66	Benign	0.02	Affected			-3	-2	-8.3	43.03
c.326G>A	S109N 2D AIThe SynGAP1 missense variant S109N is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign calls come from REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and FATHMM, while pathogenic calls come from polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves to a likely benign verdict. High‑accuracy assessments further support this: AlphaMissense‑Optimized is uncertain, and Foldetta data are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.622677	Disordered	0.669335	Binding	0.328	0.864	0.750							-5.509	Likely Benign	0.863	Likely Pathogenic	Ambiguous	0.116	Likely Benign	0.1350	0.3717											-1.45	Neutral	0.596	Possibly Damaging	0.074	Benign	3.49	Benign	0.00	Affected			1	1	-2.7	27.03
c.1589A>C	K530T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 K530T missense variant is not reported in ClinVar (ClinVar ID None) and has no entry in gnomAD (gnomAD ID None). Prediction tools that indicate a benign effect include only premPS, whereas the remaining nine tools—SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—consistently predict pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of the pathogenic‑predominant tools) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the majority of evidence points to a deleterious impact. Consequently, the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently contains no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.308712	Structured	0.018455	Uncertain	0.891	0.409	0.000							-11.506	Likely Pathogenic	0.852	Likely Pathogenic	Ambiguous	0.610	Likely Pathogenic	0.1351	0.2780		1.06	Ambiguous	0.3	1.06	Ambiguous	1.06	Ambiguous	0.27	Likely Benign	-5.17	Deleterious	0.921	Possibly Damaging	0.950	Probably Damaging	-1.63	Pathogenic	0.00	Affected			0	-1	3.2	-27.07
c.2346C>A	D782E 2D AIThe SynGAP1 missense variant D782E is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a benign majority (2 benign vs. 1 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.604312	Disordered	0.768342	Binding	0.285	0.883	0.625							-4.447	Likely Benign	0.486	Ambiguous	Likely Benign	0.127	Likely Benign	0.1351	0.7036											-1.75	Neutral	0.561	Possibly Damaging	0.207	Benign	2.14	Pathogenic	0.01	Affected			3	2	0.0	14.03
c.2346C>G	D782E 2D AIThe SynGAP1 missense variant D782E is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a majority benign vote (2 benign vs. 1 pathogenic). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact; this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.604312	Disordered	0.768342	Binding	0.285	0.883	0.625							-4.447	Likely Benign	0.486	Ambiguous	Likely Benign	0.127	Likely Benign	0.1351	0.7036											-1.75	Neutral	0.561	Possibly Damaging	0.207	Benign	2.14	Pathogenic	0.01	Affected			3	2	0.0	14.03
c.523C>G	Q175E 2D AIThe SynGAP1 missense variant Q175E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Consensus from multiple in‑silico predictors shows a benign bias: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Optimized all classify the change as benign, whereas ESM1b predicts it to be pathogenic. AlphaMissense‑Default remains uncertain. High‑accuracy assessment further supports a benign outcome: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) resolves to benign, and Foldetta stability analysis is unavailable. Consequently, the overall evidence points to a benign effect for Q175E. This conclusion is consistent with the absence of a ClinVar assertion, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.653063	Disordered	0.474689	Uncertain	0.367	0.618	0.375							-11.035	Likely Pathogenic	0.502	Ambiguous	Likely Benign	0.149	Likely Benign	0.1351	0.2028											-0.68	Neutral	0.118	Benign	0.039	Benign	4.17	Benign	0.40	Tolerated			2	2	0.0	0.98
c.1083G>C	Q361H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q361H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The remaining tools—FoldX, Rosetta, ESM1b, and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also unavailable. Overall, the majority of conventional predictors lean toward pathogenicity, while the single high‑accuracy tool suggests benign. No ClinVar annotation exists to contradict these findings. Thus, based on the collective evidence, the variant is most likely pathogenic, with no conflict with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.305330	Structured	0.427593	Uncertain	0.945	0.534	0.250							-7.269	In-Between	0.410	Ambiguous	Likely Benign	0.281	Likely Benign	0.1352	0.4151		0.68	Ambiguous	0.1	0.52	Ambiguous	0.60	Ambiguous	0.32	Likely Benign	-2.73	Deleterious	0.996	Probably Damaging	0.986	Probably Damaging	1.79	Pathogenic	0.04	Affected			3	0	0.3	9.01
c.1083G>T	Q361H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q361H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. The remaining tools—FoldX, Rosetta, ESM1b, and AlphaMissense‑Default—return uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also unavailable. Overall, the majority of conventional predictors (five pathogenic vs. three benign) lean toward a pathogenic interpretation, while the single high‑accuracy tool suggests benign. No ClinVar entry exists, so there is no contradiction with clinical database status. Based on the collective evidence, the variant is most likely pathogenic. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.305330	Structured	0.427593	Uncertain	0.945	0.534	0.250							-7.269	In-Between	0.410	Ambiguous	Likely Benign	0.281	Likely Benign	0.1352	0.4151		0.68	Ambiguous	0.1	0.52	Ambiguous	0.60	Ambiguous	0.32	Likely Benign	-2.73	Deleterious	0.996	Probably Damaging	0.986	Probably Damaging	1.79	Pathogenic	0.04	Affected			3	0	0.3	9.01
c.165G>C	Q55H 2D AIThe SynGAP1 missense variant Q55H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing clinical classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.332115	Structured	0.470108	Uncertain	0.461	0.657	0.000							-5.624	Likely Benign	0.678	Likely Pathogenic	Likely Benign	0.184	Likely Benign	0.1352	0.4143											-1.76	Neutral	0.676	Possibly Damaging	0.585	Possibly Damaging	3.81	Benign	0.00	Affected			3	0	0.3	9.01
c.165G>T	Q55H 2D AIThe SynGAP1 missense variant Q55H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicating a likely benign outcome; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.332115	Structured	0.470108	Uncertain	0.461	0.657	0.000							-5.624	Likely Benign	0.678	Likely Pathogenic	Likely Benign	0.184	Likely Benign	0.1352	0.4143											-1.76	Neutral	0.676	Possibly Damaging	0.585	Possibly Damaging	3.81	Benign	0.00	Affected			3	0	0.3	9.01
c.3032G>T	G1011V 2D AIThe SynGAP1 missense variant G1011V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.834292	Disordered	0.898380	Binding	0.332	0.869	0.625							-4.883	Likely Benign	0.129	Likely Benign	Likely Benign	0.133	Likely Benign	0.1352	0.3434											-1.21	Neutral	0.473	Possibly Damaging	0.192	Benign	2.71	Benign	0.01	Affected			-1	-3	4.6	42.08
c.3326T>G	L1109R 2D AIThe SynGAP1 missense variant L1109R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.856457	Disordered	0.948334	Binding	0.343	0.893	0.875							-5.440	Likely Benign	0.408	Ambiguous	Likely Benign	0.139	Likely Benign	0.1352	0.1919											-0.70	Neutral	0.586	Possibly Damaging	0.225	Benign	2.68	Benign	0.34	Tolerated			-3	-2	-8.3	43.03
c.3902C>G	P1301R 2D AIThe SynGAP1 missense variant P1301R is listed in ClinVar with an uncertain significance (ClinVar ID 2092739.0) and is present in gnomAD (ID 6‑33451776‑C‑G). Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign effects. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. In summary, all available predictions agree on a benign impact, and this consensus does not contradict the ClinVar uncertain status. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.885064	Binding	0.447	0.841	0.875	Uncertain		1	6-33451776-C-G	15	9.30e-6	-4.753	Likely Benign	0.162	Likely Benign	Likely Benign	0.076	Likely Benign	0.1352	0.1929											-1.13	Neutral	0.077	Benign	0.059	Benign	2.81	Benign	0.10	Tolerated	3.77	5	0	-2	-2.9	59.07
c.1177G>C	G393R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G393R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include Rosetta and premPS, whereas the remaining tools—SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default—all predict a pathogenic impact. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as uncertain. Overall, the preponderance of evidence points to a pathogenic effect. This conclusion is consistent with the lack of ClinVar annotation; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.538167	Disordered	0.402365	Uncertain	0.333	0.670	0.625							-9.148	Likely Pathogenic	0.815	Likely Pathogenic	Ambiguous	0.596	Likely Pathogenic	0.1353	0.4464		3.88	Destabilizing	1.4	-0.38	Likely Benign	1.75	Ambiguous	0.47	Likely Benign	-2.99	Deleterious	0.991	Probably Damaging	0.881	Possibly Damaging	1.32	Pathogenic	0.02	Affected			-3	-2	-4.1	99.14
c.2366C>G	P789R 2D AIThe SynGAP1 missense variant P789R is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. In contrast, the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM‑Consensus remains Likely Pathogenic; Foldetta results are unavailable. Overall, the preponderance of evidence points to a pathogenic effect, and this conclusion does not contradict the absence of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.963420	Disordered	0.541575	Binding	0.398	0.903	0.750							-2.503	Likely Benign	0.668	Likely Pathogenic	Likely Benign	0.354	Likely Benign	0.1353	0.2129											-5.04	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.03	Pathogenic	0.00	Affected			0	-2	-2.9	59.07
c.3242C>T	A1081V 2D AIThe SynGAP1 missense variant A1081V is reported in gnomAD (ID 6‑33443794‑C‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts it as pathogenic, creating a single discordant signal. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that A1081V is most likely benign, and this conclusion is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.874069	Disordered	0.979759	Binding	0.288	0.895	0.750				6-33443794-C-T			-3.973	Likely Benign	0.172	Likely Benign	Likely Benign	0.036	Likely Benign	0.1353	0.4884											-1.32	Neutral	0.611	Possibly Damaging	0.399	Benign	4.04	Benign	0.37	Tolerated	3.77	5	0	0	2.4	28.05
c.3391C>A	P1131T 2D AIThe SynGAP1 missense variant P1131T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is consistent with the lack of ClinVar annotation. Thus, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.919029	Disordered	0.855155	Binding	0.360	0.899	0.750							-4.766	Likely Benign	0.219	Likely Benign	Likely Benign	0.313	Likely Benign	0.1353	0.6315											-2.93	Deleterious	0.245	Benign	0.096	Benign	5.30	Benign	0.00	Affected			0	-1	0.9	3.99
c.910G>A	D304N 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant D304N is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM, while AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of evidence points to a benign impact, which does not contradict the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.352862	Structured	0.285053	Uncertain	0.764	0.271	0.250	Uncertain		1				-6.194	Likely Benign	0.391	Ambiguous	Likely Benign	0.345	Likely Benign	0.1353	0.7205		0.30	Likely Benign	0.1	-0.08	Likely Benign	0.11	Likely Benign	0.21	Likely Benign	-4.18	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.81	Pathogenic	0.03	Affected	3.38	23	1	2	0.0	-0.98
c.3298G>T	G1100C 2D AIThe SynGAP1 missense variant G1100C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. High‑accuracy assessments reinforce the benign trend: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates Likely Benign. Foldetta results are unavailable. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.882776	Disordered	0.972009	Binding	0.360	0.865	0.875							-6.488	Likely Benign	0.150	Likely Benign	Likely Benign	0.174	Likely Benign	0.1354	0.4768											-2.25	Neutral	0.999	Probably Damaging	0.950	Probably Damaging	1.91	Pathogenic	0.00	Affected			-3	-3	2.9	46.09
c.692T>A	F231Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant F231Y is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on benign effects include Rosetta, Foldetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. Those that predict pathogenicity are REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized; FoldX and premPS are inconclusive. High‑accuracy methods give AlphaMissense‑Optimized as pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta as benign. Overall, the majority of standard tools lean benign, but the two most accurate predictors and the consensus vote favor pathogenicity. Thus, the variant is most likely pathogenic, and this assessment does not contradict ClinVar status, which currently has no classification for F231Y. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.366687	Structured	0.306467	Uncertain	0.895	0.300	0.000							-9.831	Likely Pathogenic	0.980	Likely Pathogenic	Likely Pathogenic	0.687	Likely Pathogenic	0.1355	0.2732		0.69	Ambiguous	0.1	0.00	Likely Benign	0.35	Likely Benign	0.85	Ambiguous	-2.60	Deleterious	0.437	Benign	0.079	Benign	5.50	Benign	0.12	Tolerated			7	3	-4.1	16.00
c.1765A>G	I589V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 I589V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include PROVEAN, SIFT, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, polyPhen‑2 (HumDiv and HumVar), and FATHMM. The remaining tools—FoldX, Rosetta, Foldetta, premPS, and AlphaMissense‑Default—return uncertain or inconclusive results. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign; and Foldetta is uncertain. Taken together, the majority of evidence, including the high‑accuracy predictions, points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation and does not contradict any existing clinical database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.018415	Structured	0.084536	Uncertain	0.927	0.214	0.000							-6.966	Likely Benign	0.464	Ambiguous	Likely Benign	0.535	Likely Pathogenic	0.1356	0.3568		0.98	Ambiguous	0.0	0.78	Ambiguous	0.88	Ambiguous	0.96	Ambiguous	-1.00	Neutral	0.969	Probably Damaging	0.960	Probably Damaging	-1.50	Pathogenic	0.31	Tolerated			4	3	-0.3	-14.03
c.2699C>T	T900M 2D AIThe SynGAP1 missense variant T900M is listed in ClinVar (ID 1063691.0) with an “Uncertain” clinical significance and is present in the gnomAD database (gnomAD ID 6‑33443251‑C‑T). Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign effects. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, which does not contradict the ClinVar “Uncertain” status. Thus, the variant is most likely benign. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.675549	Disordered	0.465347	Uncertain	0.289	0.924	0.375	Conflicting		2	6-33443251-C-T	14	8.68e-6	-3.852	Likely Benign	0.176	Likely Benign	Likely Benign	0.015	Likely Benign	0.1356	0.6533											-0.81	Neutral	0.060	Benign	0.016	Benign	2.79	Benign	0.08	Tolerated	4.32	4	-1	-1	2.6	30.09
c.2143C>A	P715T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P715T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split assessment: benign predictions come from REVEL, Rosetta, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic predictions arise from FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and the SGM‑Consensus. Two tools, Foldetta and premPS, returned uncertain results. High‑accuracy analyses further clarify the picture: AlphaMissense‑Optimized predicts a benign effect, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates pathogenicity; Foldetta remains inconclusive. Overall, the majority of evidence points toward a pathogenic impact, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.243554	Structured	0.409757	Uncertain	0.956	0.362	0.000							-10.501	Likely Pathogenic	0.744	Likely Pathogenic	Likely Benign	0.368	Likely Benign	0.1357	0.4072		2.55	Destabilizing	0.1	0.29	Likely Benign	1.42	Ambiguous	0.72	Ambiguous	-7.23	Deleterious	1.000	Probably Damaging	0.993	Probably Damaging	3.37	Benign	0.01	Affected			0	-1	0.9	3.99
c.2165G>C	S722T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S722T is reported in gnomAD (6‑33441630‑G‑C) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only polyPhen‑2 HumDiv predicts it as pathogenic, while FoldX is uncertain. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign; and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also predicts benign. No prediction or stability result is missing or inconclusive. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.468512	Structured	0.457186	Uncertain	0.950	0.431	0.375				6-33441630-G-C	1	6.20e-7	-5.734	Likely Benign	0.202	Likely Benign	Likely Benign	0.118	Likely Benign	0.1357	0.4363		0.53	Ambiguous	0.0	-0.32	Likely Benign	0.11	Likely Benign	-0.12	Likely Benign	-0.57	Neutral	0.921	Possibly Damaging	0.414	Benign	2.57	Benign	1.00	Tolerated	3.50	8	1	1	0.1	14.03
c.2783A>G	Q928R 2D AIThe SynGAP1 missense variant Q928R is listed in gnomAD (ID 6‑33443335‑A‑G) but has no ClinVar entry. Functional prediction tools fall into two consensus groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). AlphaMissense‑Optimized returns an uncertain result, and no Foldetta (FoldX‑MD/Rosetta stability) data are available. High‑accuracy assessments therefore indicate a likely pathogenic outcome (SGM‑Consensus) with no contradictory evidence from ClinVar. Based on the preponderance of pathogenic predictions, the variant is most likely pathogenic, and this assessment does not conflict with the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.986260	Binding	0.324	0.852	0.250				6-33443335-A-G	1	6.20e-7	-4.089	Likely Benign	0.826	Likely Pathogenic	Ambiguous	0.290	Likely Benign	0.1357	0.3453											-2.91	Deleterious	0.994	Probably Damaging	0.988	Probably Damaging	1.58	Pathogenic	0.00	Affected	4.32	4	1	1	-1.0	28.06
c.3383G>T	G1128V 2D AIThe SynGAP1 missense variant G1128V is reported in gnomAD (variant ID 6‑33443935‑G‑T) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags it as pathogenic, creating a single discordant call. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence indicates the variant is most likely benign, and this conclusion is not contradicted by any ClinVar classification (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.896620	Disordered	0.865136	Binding	0.309	0.911	0.875				6-33443935-G-T			-5.111	Likely Benign	0.081	Likely Benign	Likely Benign	0.399	Likely Benign	0.1358	0.3922											-0.69	Neutral	0.611	Possibly Damaging	0.185	Benign	4.39	Benign	0.09	Tolerated	4.32	4	-3	-1	4.6	42.08
c.1294T>C	C432R 2D 3DClick to see structure in 3D Viewer AIClinVar has no entry for this SynGAP1 missense variant, and it is absent from gnomAD. Prediction tools that agree on a benign effect include only FATHMM. The majority of algorithms predict a pathogenic impact: REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). FoldX and Foldetta report uncertain results. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is pathogenic, the SGM‑Consensus is likely pathogenic, while Foldetta remains inconclusive. Overall, the consensus of the available predictions indicates that the variant is most likely pathogenic, and this assessment does not contradict the ClinVar status, which currently has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.111485	Structured	0.362533	Uncertain	0.960	0.285	0.000							-13.858	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.690	Likely Pathogenic	0.1359	0.1766		1.03	Ambiguous	0.2	2.05	Destabilizing	1.54	Ambiguous	1.73	Destabilizing	-11.46	Deleterious	0.999	Probably Damaging	0.993	Probably Damaging	3.45	Benign	0.01	Affected			-4	-3	-7.0	53.05
c.3041G>T	G1014V 2D AIThe SynGAP1 missense variant G1014V is listed in ClinVar (ID 809922.0) with an “Uncertain” status and is not reported in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv indicates a pathogenic outcome, while the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign effect, which does not contradict the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.771762	Disordered	0.914808	Binding	0.293	0.835	0.625	Uncertain		1				-4.612	Likely Benign	0.181	Likely Benign	Likely Benign	0.053	Likely Benign	0.1359	0.3533											-2.47	Neutral	0.818	Possibly Damaging	0.377	Benign	2.72	Benign	0.06	Tolerated	3.77	5	-1	-3	4.6	42.08
c.1711T>A	S571T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S571T is not reported in ClinVar (ClinVar ID: None) and has no entry in gnomAD (gnomAD ID: None). Prediction tools that indicate a benign effect include FoldX, Rosetta, Foldetta, premPS, SIFT, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SGM‑Consensus, REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM; AlphaMissense‑Default remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as benign. Overall, the majority of tools (seven) predict pathogenicity, while six predict benignity, and the high‑accuracy subset is split. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.069024	Structured	0.045569	Uncertain	0.928	0.270	0.000							-8.243	Likely Pathogenic	0.431	Ambiguous	Likely Benign	0.564	Likely Pathogenic	0.1360	0.4014		0.37	Likely Benign	0.1	-0.21	Likely Benign	0.08	Likely Benign	0.25	Likely Benign	-2.76	Deleterious	0.933	Possibly Damaging	0.933	Probably Damaging	-1.25	Pathogenic	0.10	Tolerated			1	1	0.1	14.03
c.2816C>G	P939R 2D AIThe SynGAP1 missense variant P939R is reported in gnomAD (ID 6‑33443368‑C‑G) but has no ClinVar entry. Functional prediction tools show mixed results: benign calls come from REVEL, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. Grouping by consensus, the benign‑predicted tools outnumbered the pathogenic ones by one, but the overall tally favors pathogenicity (5 pathogenic vs 4 benign). High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is benign, but the SGM Consensus (a 2‑vs‑2 majority among AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) yields no clear verdict, and Foldetta data are unavailable. Consequently, the variant is most likely pathogenic according to the available predictions, and this assessment does not contradict any ClinVar status because none is reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.894241	Disordered	0.935841	Binding	0.397	0.897	0.625				6-33443368-C-G	1	6.20e-7	-4.863	Likely Benign	0.260	Likely Benign	Likely Benign	0.199	Likely Benign	0.1360	0.3336											-3.79	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.18	Pathogenic	0.00	Affected	3.77	5	-2	0	-2.9	59.07
c.3359G>T	G1120V 2D AIThe SynGAP1 missense variant G1120V is catalogued in gnomAD (6‑33443911‑G‑T) but has no ClinVar entry. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all score the variant as benign, while ESM1b remains uncertain. No tool predicts pathogenicity. The high‑accuracy consensus, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN), classifies the variant as “Likely Benign.” AlphaMissense‑Optimized also reports a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the evidence strongly supports a benign classification, and this assessment does not contradict any ClinVar status, as none is assigned. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.871313	Disordered	0.804931	Binding	0.335	0.925	0.875				6-33443911-G-T			-7.659	In-Between	0.081	Likely Benign	Likely Benign	0.355	Likely Benign	0.1360	0.3694											-1.20	Neutral	0.292	Benign	0.157	Benign	3.61	Benign	0.06	Tolerated	3.77	5	-3	-1	4.6	42.08
c.3415C>G	Q1139E 2D AIThe SynGAP1 missense variant Q1139E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign or likely benign outcome, whereas only SIFT classifies it as pathogenic. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates likely benign. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the consensus of the available predictions points to a benign effect, and this is consistent with the lack of ClinVar evidence for pathogenicity. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.908098	Disordered	0.721191	Binding	0.313	0.866	1.000							-3.065	Likely Benign	0.204	Likely Benign	Likely Benign	0.285	Likely Benign	0.1360	0.2269											-1.34	Neutral	0.112	Benign	0.089	Benign	5.36	Benign	0.00	Affected			2	2	0.0	0.98
c.3892C>A	Q1298K 2D AIThe SynGAP1 missense variant Q1298K is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the consensus of all available predictions points to a benign impact, and this conclusion is not contradicted by any ClinVar status, as no ClinVar entry exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.823549	Disordered	0.895297	Binding	0.410	0.821	0.750							-3.415	Likely Benign	0.228	Likely Benign	Likely Benign	0.138	Likely Benign	0.1360	0.2903											-0.27	Neutral	0.000	Benign	0.002	Benign	2.86	Benign	0.24	Tolerated			1	1	-0.4	0.04
c.1027G>C	V343L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant V343L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) all predict benign or likely benign. Only FATHMM predicts a pathogenic outcome, while FoldX and Rosetta provide uncertain results and are therefore not considered decisive. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized scores benign, the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also indicates benign. Overall, the majority of evidence supports a benign classification, and this is consistent with the absence of ClinVar reporting. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.291804	Structured	0.383911	Uncertain	0.882	0.497	0.250							-6.268	Likely Benign	0.310	Likely Benign	Likely Benign	0.033	Likely Benign	0.1361	0.5008		-0.93	Ambiguous	0.2	0.66	Ambiguous	-0.14	Likely Benign	0.16	Likely Benign	-1.09	Neutral	0.005	Benign	0.013	Benign	2.12	Pathogenic	0.64	Tolerated			2	1	-0.4	14.03
c.1945A>C	M649L 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant M649L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, FoldX, Rosetta, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized; pathogenic predictions arise from PROVEAN and AlphaMissense‑Default, while premPS remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split, and Foldetta predicts benign stability. Overall, the preponderance of evidence points to a benign effect. This conclusion is consistent with the absence of a ClinVar assertion, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.051831	Structured	0.360413	Uncertain	0.962	0.345	0.000							-5.210	Likely Benign	0.745	Likely Pathogenic	Likely Benign	0.294	Likely Benign	0.1361	0.4025		0.19	Likely Benign	0.4	0.26	Likely Benign	0.23	Likely Benign	0.64	Ambiguous	-2.99	Deleterious	0.009	Benign	0.007	Benign	3.73	Benign	0.15	Tolerated			4	2	1.9	-18.03
c.1945A>T	M649L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M649L is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN and AlphaMissense‑Default, while premPS remains uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta (combining FoldX‑MD and Rosetta outputs) as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.051831	Structured	0.360413	Uncertain	0.962	0.345	0.000							-5.210	Likely Benign	0.745	Likely Pathogenic	Likely Benign	0.294	Likely Benign	0.1361	0.4025		0.19	Likely Benign	0.4	0.26	Likely Benign	0.23	Likely Benign	0.64	Ambiguous	-2.99	Deleterious	0.009	Benign	0.007	Benign	3.73	Benign	0.15	Tolerated			4	2	1.9	-18.03
c.3571C>T	R1191W 2D AIThe SynGAP1 missense variant R1191W is not reported in ClinVar (ClinVar ID None) but is present in gnomAD (ID 6‑33444606‑C‑T). Functional prediction tools split in their assessment: benign predictions come from REVEL, ESM1b, and FATHMM, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy analyses show AlphaMissense‑Optimized classifying the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two pathogenic vs two benign votes), and Foldetta results are unavailable. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar annotation (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.661982	Disordered	0.439584	Uncertain	0.765	0.622	0.625				6-33444606-C-T	4	2.48e-6	-4.839	Likely Benign	0.987	Likely Pathogenic	Likely Pathogenic	0.320	Likely Benign	0.1361	0.3328											-3.16	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	2.61	Benign	0.01	Affected	3.82	4	-3	2	3.6	30.03
c.1111A>C	S371R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change S371R is catalogued in gnomAD (ID 6‑33438016‑A‑C) but has no ClinVar entry. Functional prediction programs largely agree on a benign effect: REVEL, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, Foldetta, and the SGM‑Consensus score (Likely Benign) all report a non‑pathogenic outcome. Only AlphaMissense‑Default predicts a pathogenic effect, while FoldX and premPS are inconclusive. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta) is benign. Taken together, the majority of evidence supports a benign classification, and this is consistent with the absence of a ClinVar pathogenic report. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.444081	Structured	0.432086	Uncertain	0.294	0.746	0.375				6-33438016-A-C			-6.415	Likely Benign	0.762	Likely Pathogenic	Likely Benign	0.295	Likely Benign	0.1362	0.4131		0.51	Ambiguous	1.2	-0.25	Likely Benign	0.13	Likely Benign	0.57	Ambiguous	-1.17	Neutral	0.396	Benign	0.099	Benign	5.35	Benign	0.26	Tolerated	3.52	18	-1	0	-3.7	69.11
c.1113T>A	S371R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S371R is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools largely agree on a benign effect: SGM‑Consensus, REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all classify the substitution as benign, while AlphaMissense‑Optimized also predicts benign. Only AlphaMissense‑Default indicates a pathogenic outcome; FoldX and premPS are inconclusive. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. Overall, the majority of evidence supports a benign impact, and this is consistent with the absence of a ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.444081	Structured	0.432086	Uncertain	0.294	0.746	0.375							-6.415	Likely Benign	0.762	Likely Pathogenic	Likely Benign	0.344	Likely Benign	0.1362	0.4131		0.51	Ambiguous	1.2	-0.25	Likely Benign	0.13	Likely Benign	0.57	Ambiguous	-1.17	Neutral	0.396	Benign	0.099	Benign	5.35	Benign	0.26	Tolerated	3.52	18	-1	0	-3.7	69.11
c.1113T>G	S371R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S371R is reported in gnomAD (variant ID 6‑33438018‑T‑G) but has no ClinVar entry. Prediction tools that agree on a benign effect include REVEL, Rosetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Only AlphaMissense‑Default predicts a pathogenic outcome. The SGM‑Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, resolves as “Likely Benign” (3 benign vs. 1 pathogenic). High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, the SGM‑Consensus is benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. No prediction or stability result is missing or inconclusive. Overall, the evidence strongly favors a benign classification, and this is consistent with the absence of a ClinVar pathogenic report. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.444081	Structured	0.432086	Uncertain	0.294	0.746	0.375				6-33438018-T-G	1	1.18e-6	-6.415	Likely Benign	0.762	Likely Pathogenic	Likely Benign	0.340	Likely Benign	0.1362	0.4131		0.51	Ambiguous	1.2	-0.25	Likely Benign	0.13	Likely Benign	0.57	Ambiguous	-1.17	Neutral	0.396	Benign	0.099	Benign	5.35	Benign	0.26	Tolerated	3.52	18	-1	0	-3.7	69.11
c.3368G>T	G1123V 2D AIThe SynGAP1 missense variant G1123V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; ESM1b is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the collective predictions strongly suggest that G1123V is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.837511	Disordered	0.827246	Binding	0.346	0.934	0.875							-7.129	In-Between	0.091	Likely Benign	Likely Benign	0.333	Likely Benign	0.1362	0.3694											-1.03	Neutral	0.292	Benign	0.157	Benign	4.35	Benign	0.29	Tolerated			-1	-3	4.6	42.08
c.901G>A	A301T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A301T is listed in ClinVar with an “Uncertain” status and is present in gnomAD (ID 6‑33437806‑G‑A). Prediction tools that uniformly indicate a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign”; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, is benign. Overall, the majority of evidence points to a benign effect, and this is not in conflict with the ClinVar “Uncertain” classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.429200	Structured	0.258424	Uncertain	0.647	0.272	0.375	Uncertain		5	6-33437806-G-A	2	1.24e-6	-3.448	Likely Benign	0.070	Likely Benign	Likely Benign	0.150	Likely Benign	0.1362	0.7201		0.36	Likely Benign	0.2	-0.33	Likely Benign	0.02	Likely Benign	0.03	Likely Benign	-0.25	Neutral	0.997	Probably Damaging	0.989	Probably Damaging	4.15	Benign	0.22	Tolerated	4.32	14	1	0	-2.5	30.03	219.8	-42.8	-0.1	0.0	-0.5	0.2								Uncertain	The methyl group of Ala301, located in a β hairpin loop linking two anti-parallel β sheet strands (res. Met289-Pro298, res. Thr305-Asn315), points outward from the β hairpin loop, and its backbone atoms do not participate in the loop formation in the WT simulations. In the variant simulations, the hydroxyl group of the Thr301 side chain also mostly points outward; however, the guanidinium group of Arg299 is moved away from its central hairpin loop position.β hairpins are potential nucleation sites during the initial stages of protein folding, so even minor changes in them could be significant. Due to its location near the membrane surface, the residue swap could also affect the C2 loop dynamics and SynGAP-membrane association. However, this is beyond the scope of the solvent-only simulations to unravel.
c.2158G>C	D720H 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 D720H missense variant is not reported in ClinVar and has no entries in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Foldetta, and premPS. Tools that predict a pathogenic effect comprise PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and the SGM Consensus, which is a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN and is labeled Likely Pathogenic. The high‑accuracy AlphaMissense‑Optimized score is Uncertain, while Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, indicates a Benign effect. Considering the overall distribution of predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.374039	Structured	0.450695	Uncertain	0.955	0.417	0.125							-12.355	Likely Pathogenic	0.947	Likely Pathogenic	Ambiguous	0.444	Likely Benign	0.1363	0.6198		0.03	Likely Benign	0.0	-0.87	Ambiguous	-0.42	Likely Benign	0.48	Likely Benign	-5.27	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.13	Pathogenic	0.01	Affected			1	-1	0.3	22.05
c.2197C>G	Q733E 2D AIThe SynGAP1 missense variant Q733E is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign predictions from REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized; pathogenic predictions from polyPhen‑2 (HumDiv and HumVar) and SIFT; ESM1b is uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus itself is Benign. Foldetta results are not available, so they do not influence the assessment. Overall, the majority of evidence points to a benign effect, and this conclusion is consistent with the absence of ClinVar pathogenic reports. Thus, the variant is most likely benign, and this is not contradictory to ClinVar, which has no pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.874069	Disordered	0.410831	Uncertain	0.331	0.686	0.875							-7.651	In-Between	0.152	Likely Benign	Likely Benign	0.117	Likely Benign	0.1363	0.1130											-1.38	Neutral	0.983	Probably Damaging	0.637	Possibly Damaging	2.60	Benign	0.03	Affected			2	2	0.0	0.98
c.2426G>A	S809N 2D AIThe SynGAP1 missense variant S809N is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a pathogenic impact, while AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign outcome. High‑accuracy assessments further support this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus itself is benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign effect for S809N, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	SH3-binding motif	0.626927	Disordered	0.853218	Binding	0.330	0.907	0.500							-5.308	Likely Benign	0.341	Ambiguous	Likely Benign	0.079	Likely Benign	0.1363	0.5028											-1.12	Neutral	0.784	Possibly Damaging	0.316	Benign	2.51	Benign	0.04	Affected			1	1	-2.7	27.03
c.2470A>T	S824C 2D AIThe SynGAP1 missense variant S824C is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also as benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for S824C, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.728858	Disordered	0.611272	Binding	0.314	0.884	0.750							-6.613	Likely Benign	0.730	Likely Pathogenic	Likely Benign	0.108	Likely Benign	0.1363	0.6277											-1.87	Neutral	1.000	Probably Damaging	0.998	Probably Damaging	2.57	Benign	0.07	Tolerated			0	-1	3.3	16.06
c.3681A>C	E1227D 2D AIThe SynGAP1 missense variant E1227D is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority of the high‑accuracy tools) also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence, including the high‑accuracy tools, points to the variant being most likely benign, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.513880	Disordered	0.433399	Uncertain	0.860	0.544	0.500							-5.675	Likely Benign	0.777	Likely Pathogenic	Likely Benign	0.172	Likely Benign	0.1363	0.4161											-1.67	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	2.60	Benign	0.00	Affected			3	2	0.0	-14.03
c.3681A>T	E1227D 2D AIThe SynGAP1 missense variant E1227D is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, while pathogenic predictions come from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Benign. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority of the high‑accuracy tools) also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence, including the high‑accuracy tools, points to the variant being most likely benign, and this conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.513880	Disordered	0.433399	Uncertain	0.860	0.544	0.500							-5.675	Likely Benign	0.777	Likely Pathogenic	Likely Benign	0.170	Likely Benign	0.1363	0.4161											-1.67	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	2.60	Benign	0.00	Affected			3	2	0.0	-14.03
c.3703A>C	M1235L 2D AIThe SynGAP1 missense variant M1235L is reported as “Likely Benign” by the SGM‑Consensus method and has no ClinVar entry, indicating it has not been classified in that database. It is also absent from gnomAD, so its allele frequency is not documented there. Across the spectrum of in‑silico predictors, all tools that provide a verdict—REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—concur that the substitution is benign; none predict pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized scores benign, and the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates benign. Foldetta, a protein‑folding stability predictor, has no available result for this variant. Based on the unanimous benign predictions and the lack of ClinVar classification, the variant is most likely benign, with no contradiction to existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.690604	Disordered	0.577958	Binding	0.872	0.532	0.125							-2.013	Likely Benign	0.062	Likely Benign	Likely Benign	0.067	Likely Benign	0.1363	0.3935											-0.38	Neutral	0.001	Benign	0.002	Benign	2.89	Benign	1.00	Tolerated			4	2	1.9	-18.03
c.3703A>T	M1235L 2D AIThe SynGAP1 missense variant M1235L is reported as “Likely Benign” in the SGM‑Consensus and has no ClinVar entry, and it is not listed in gnomAD. All available in‑silico predictors classify the substitution as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely benign. Foldetta results are not available. Based on the unanimous benign predictions and lack of ClinVar or gnomAD evidence, the variant is most likely benign, with no contradiction to ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.690604	Disordered	0.577958	Binding	0.872	0.532	0.125							-2.013	Likely Benign	0.062	Likely Benign	Likely Benign	0.067	Likely Benign	0.1363	0.3935											-0.38	Neutral	0.001	Benign	0.002	Benign	2.89	Benign	1.00	Tolerated			4	2	1.9	-18.03
c.467T>A	F156Y 2D AIThe SynGAP1 missense variant F156Y is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and FATHMM, whereas a majority of tools (polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is a tie (2 pathogenic vs. 2 benign) and thus unavailable; Foldetta predictions are not provided. Overall, the balance of evidence (5 pathogenic vs. 3 benign predictions) indicates that the variant is most likely pathogenic, and this conclusion does not contradict any existing ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.476583	Structured	0.521964	Binding	0.284	0.785	0.500							-11.811	Likely Pathogenic	0.869	Likely Pathogenic	Ambiguous	0.136	Likely Benign	0.1363	0.1419											-1.51	Neutral	0.981	Probably Damaging	0.931	Probably Damaging	3.96	Benign	0.00	Affected			7	3	-4.1	16.00
c.566C>G	P189R 2D AIThe SynGAP1 missense variant P189R has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two groups: benign predictions come from REVEL and FATHMM, whereas the remaining eight tools—PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus—indicate pathogenicity. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is labeled Likely Pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus confirms a likely pathogenic status. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a pathogenic effect for P189R, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.428590	Uncertain	0.331	0.602	0.250							-13.503	Likely Pathogenic	0.997	Likely Pathogenic	Likely Pathogenic	0.331	Likely Benign	0.1363	0.3894											-6.45	Deleterious	0.997	Probably Damaging	0.916	Probably Damaging	4.05	Benign	0.01	Affected			0	-2	-2.9	59.07
c.2305C>G	L769V 2D AIThe SynGAP1 missense variant L769V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv flags it as pathogenic, but this is the sole discordant call. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” consensus. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.411940	Structured	0.928432	Binding	0.367	0.883	0.250							-4.585	Likely Benign	0.106	Likely Benign	Likely Benign	0.075	Likely Benign	0.1364	0.2558											-0.41	Neutral	0.625	Possibly Damaging	0.249	Benign	4.04	Benign	0.25	Tolerated			2	1	0.4	-14.03
c.2102C>G	P701R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 P701R missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, ESM1b, and AlphaMissense‑Default. Two tools (FoldX and premPS) give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, Foldetta (combining FoldX‑MD and Rosetta outputs) as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 2‑to‑2 split. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation because none exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.074921	Structured	0.404318	Uncertain	0.918	0.345	0.000							-11.060	Likely Pathogenic	0.779	Likely Pathogenic	Likely Benign	0.088	Likely Benign	0.1365	0.2500		0.54	Ambiguous	0.0	-0.19	Likely Benign	0.18	Likely Benign	0.65	Ambiguous	-2.09	Neutral	0.784	Possibly Damaging	0.278	Benign	3.41	Benign	0.08	Tolerated			0	-2	-2.9	59.07
c.765C>A	D255E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense change D255E is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include premPS, SIFT, ESM1b, and FATHMM. Those that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. FoldX, Rosetta, and Foldetta give uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta is also inconclusive. Overall, the majority of available predictions (seven pathogenic vs. four benign) point to a likely pathogenic impact. This conclusion does not contradict the ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.501700	Disordered	0.219132	Uncertain	0.801	0.273	0.250							-6.876	Likely Benign	0.989	Likely Pathogenic	Likely Pathogenic	0.508	Likely Pathogenic	0.1365	0.5067		0.80	Ambiguous	0.3	0.90	Ambiguous	0.85	Ambiguous	0.15	Likely Benign	-2.98	Deleterious	0.994	Probably Damaging	0.978	Probably Damaging	5.89	Benign	0.08	Tolerated			3	2	0.0	14.03
c.765C>G	D255E 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant D255E is not reported in ClinVar (ClinVar status: none) and is absent from gnomAD (gnomAD ID: none). Prediction tools that agree on a benign effect include premPS, SIFT, ESM1b, and FATHMM, whereas those that agree on a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. The remaining tools (FoldX, Rosetta, Foldetta) provide uncertain results. High‑accuracy assessments show AlphaMissense‑Optimized predicts pathogenicity; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 pathogenic vs. 2 benign), and Foldetta is also inconclusive. Overall, the majority of available predictions (7 pathogenic vs. 4 benign) indicate a pathogenic effect. Thus, the variant is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.501700	Disordered	0.219132	Uncertain	0.801	0.273	0.250							-6.876	Likely Benign	0.989	Likely Pathogenic	Likely Pathogenic	0.509	Likely Pathogenic	0.1365	0.5067		0.80	Ambiguous	0.3	0.90	Ambiguous	0.85	Ambiguous	0.15	Likely Benign	-2.98	Deleterious	0.994	Probably Damaging	0.978	Probably Damaging	5.89	Benign	0.08	Tolerated			3	2	0.0	14.03
c.2138C>G	P713R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P713R has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, and FATHMM. Those that predict a pathogenic effect are SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default. The remaining tools, premPS and AlphaMissense‑Optimized, are inconclusive. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) as Benign. Overall, the majority of predictions lean toward pathogenicity, while the most accurate methods give conflicting results. Thus, the variant is most likely pathogenic based on the current evidence, and this assessment does not contradict ClinVar status, which has no classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.271506	Structured	0.393235	Uncertain	0.961	0.371	0.000							-12.101	Likely Pathogenic	0.930	Likely Pathogenic	Ambiguous	0.331	Likely Benign	0.1366	0.2335		0.29	Likely Benign	0.0	0.21	Likely Benign	0.25	Likely Benign	0.86	Ambiguous	-7.42	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.29	Benign	0.00	Affected			0	-2	-2.9	59.07
c.2755C>G	Q919E 2D AIThe SynGAP1 missense variant Q919E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a “Likely Benign” classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of high‑confidence predictions and the consensus score favor a benign impact. Thus, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.618285	Disordered	0.911223	Binding	0.299	0.841	0.250							-3.352	Likely Benign	0.157	Likely Benign	Likely Benign	0.143	Likely Benign	0.1366	0.2692											-1.13	Neutral	0.771	Possibly Damaging	0.492	Possibly Damaging	2.44	Pathogenic	0.05	Affected			2	2	0.0	0.98
c.3101C>G	P1034R 2D AIThe SynGAP1 P1034R variant has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are PROVEAN, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, while the SGM Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports it as Likely Pathogenic; Foldetta stability analysis is unavailable. Overall, the predictions are mixed, with a slight tilt toward pathogenicity due to the SGM Consensus result and the number of pathogenic calls. The variant is most likely pathogenic based on the current computational evidence, and this assessment does not contradict ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.926919	Disordered	0.991713	Binding	0.343	0.752	0.625							-3.666	Likely Benign	0.676	Likely Pathogenic	Likely Benign	0.073	Likely Benign	0.1366	0.4182											-3.04	Deleterious	0.002	Benign	0.005	Benign	2.40	Pathogenic	0.02	Affected			0	-2	-2.9	59.07
c.3377G>T	G1126V 2D AIThe SynGAP1 missense variant G1126V is listed in ClinVar with an uncertain significance and is present in the gnomAD database. Consensus from multiple in‑silico predictors indicates a benign effect: REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score all classify the change as benign. Only the SIFT algorithm predicts a pathogenic outcome. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized reports a benign effect, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates likely benign, while Foldetta’s protein‑folding stability analysis is unavailable. Overall, the preponderance of evidence points to a benign variant, which is consistent with the ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.894241	Disordered	0.837209	Binding	0.345	0.918	0.875	Uncertain		1	6-33443929-G-T			-6.536	Likely Benign	0.089	Likely Benign	Likely Benign	0.357	Likely Benign	0.1366	0.3884											-1.20	Neutral	0.009	Benign	0.008	Benign	4.76	Benign	0.03	Affected	3.77	5	-1	-3	4.6	42.08
c.3466G>A	A1156T 2D AIThe SynGAP1 missense variant A1156T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized classifies the variant as pathogenic, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Pathogenic. No Foldetta stability prediction is available for this variant. Overall, the preponderance of evidence from multiple in silico tools points to a pathogenic effect for A1156T, and this conclusion does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.720929	Disordered	0.871395	Binding	0.294	0.861	0.500							-3.732	Likely Benign	0.988	Likely Pathogenic	Likely Pathogenic	0.285	Likely Benign	0.1366	0.7442											-2.99	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	1.63	Pathogenic	0.00	Affected			1	0	-2.5	30.03
c.3896T>G	L1299R 2D AIThe SynGAP1 missense variant L1299R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (which is “Likely Benign”). Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact for this variant, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.771762	Disordered	0.896323	Binding	0.398	0.832	0.750							-3.080	Likely Benign	0.260	Likely Benign	Likely Benign	0.293	Likely Benign	0.1366	0.1147											-3.75	Deleterious	0.971	Probably Damaging	0.597	Possibly Damaging	2.68	Benign	0.01	Affected			-3	-2	-8.3	43.03
c.572G>A	S191N 2D AIThe SynGAP1 missense variant S191N is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, and FATHMM, while those that predict a pathogenic effect are polyPhen‑2 HumDiv, SIFT, and AlphaMissense‑Default. Two tools report an uncertain outcome: ESM1b and AlphaMissense‑Optimized. High‑accuracy assessment shows that the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans toward benign (2 benign vs. 1 pathogenic). AlphaMissense‑Optimized remains uncertain, and Foldetta folding‑stability analysis is unavailable. Overall, the preponderance of evidence points to a benign impact for S191N, and this conclusion does not contradict any ClinVar annotation, as the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.429200	Structured	0.428475	Uncertain	0.322	0.615	0.125							-7.887	In-Between	0.830	Likely Pathogenic	Ambiguous	0.148	Likely Benign	0.1366	0.5898											-2.21	Neutral	0.596	Possibly Damaging	0.260	Benign	3.78	Benign	0.03	Affected			1	1	-2.7	27.03
c.739C>A	Q247K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant Q247K (PH domain) is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include FoldX, premPS, PROVEAN, SIFT, FATHMM, AlphaMissense‑Optimized, and polyPhen2_HumVar. Tools that predict a pathogenic effect are REVEL, polyPhen2_HumDiv, and ESM1b. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, favors a benign outcome (2 benign vs. 1 pathogenic). High‑accuracy methods all support benignity: AlphaMissense‑Optimized is benign, the SGM Consensus is benign, and Foldetta (combining FoldX‑MD and Rosetta) is benign. Uncertain results from AlphaMissense‑Default and Rosetta are treated as unavailable. Overall, the collective evidence points to a benign impact for Q247K, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		PH	0.490133	Structured	0.283012	Uncertain	0.822	0.339	0.250							-10.377	Likely Pathogenic	0.502	Ambiguous	Likely Benign	0.529	Likely Pathogenic	0.1366	0.2758		-0.28	Likely Benign	0.1	0.74	Ambiguous	0.23	Likely Benign	-0.13	Likely Benign	-0.44	Neutral	0.787	Possibly Damaging	0.351	Benign	5.89	Benign	0.13	Tolerated			1	1	-0.4	0.04
c.1582C>A	P528T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P528T is not reported in ClinVar (ClinVar status: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), REVEL, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. No tools predict a benign outcome. Predictions that are uncertain or inconclusive are Rosetta, Foldetta, premPS, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta as Uncertain. Based on the preponderance of pathogenic predictions and the lack of benign evidence, the variant is most likely pathogenic. This conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.225814	Structured	0.020396	Uncertain	0.909	0.403	0.000							-13.782	Likely Pathogenic	0.798	Likely Pathogenic	Ambiguous	0.673	Likely Pathogenic	0.1367	0.4360		2.05	Destabilizing	0.3	1.01	Ambiguous	1.53	Ambiguous	0.66	Ambiguous	-7.69	Deleterious	1.000	Probably Damaging	0.996	Probably Damaging	2.49	Pathogenic	0.00	Affected			0	-1	0.9	3.99
c.2954G>T	S985I 2D AIThe SynGAP1 missense variant S985I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect are REVEL and FATHMM, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. ESM1b remains uncertain. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a pathogenic verdict (2 pathogenic vs. 1 benign). Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates that S985I is most likely pathogenic, and this conclusion does not contradict any ClinVar annotation because no ClinVar status exists for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.720929	Disordered	0.941547	Binding	0.302	0.896	0.750							-7.858	In-Between	0.971	Likely Pathogenic	Likely Pathogenic	0.131	Likely Benign	0.1367	0.5206											-2.78	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	2.50	Benign	0.00	Affected			-1	-2	5.3	26.08
c.964G>A	A322T 2D AIThe SynGAP1 missense variant A322T is not reported in ClinVar and is absent from gnomAD. Consensus from most in silico predictors classifies the change as benign: SGM‑Consensus (Likely Benign), REVEL, Rosetta, Foldetta, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a neutral effect. Only FATHMM indicates a pathogenic signal, while FoldX and premPS are inconclusive. High‑accuracy assessments reinforce the benign interpretation: AlphaMissense‑Optimized scores benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also reports Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts a benign impact on protein stability. Overall, the majority of evidence supports a benign effect for A322T, and this is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	C2	0.175930	Structured	0.425745	Uncertain	0.938	0.334	0.000							-2.252	Likely Benign	0.064	Likely Benign	Likely Benign	0.112	Likely Benign	0.1367	0.6432		0.58	Ambiguous	0.9	0.22	Likely Benign	0.40	Likely Benign	-0.52	Ambiguous	0.20	Neutral	0.010	Benign	0.005	Benign	1.95	Pathogenic	0.73	Tolerated			1	0	-2.5	30.03
c.1431G>A	M477I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M477I is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Optimized. Only FATHMM predicts a pathogenic outcome, while FoldX, Foldetta, and AlphaMissense‑Default are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as benign, and Foldetta as uncertain. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation and gnomAD presence, indicating no contradiction with existing database status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.268042	Structured	0.408680	Uncertain	0.761	0.250	0.000							-2.662	Likely Benign	0.467	Ambiguous	Likely Benign	0.291	Likely Benign	0.1368	0.3176		0.72	Ambiguous	0.1	0.36	Likely Benign	0.54	Ambiguous	0.45	Likely Benign	-1.57	Neutral	0.000	Benign	0.001	Benign	-1.21	Pathogenic	0.09	Tolerated			2	1	2.6	-18.03
c.1431G>C	M477I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M477I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Optimized all predict benign. Only FATHMM predicts pathogenic, while FoldX, Foldetta, and AlphaMissense‑Default are uncertain. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign, and Foldetta remains uncertain. Overall, the majority of evidence supports a benign impact, and this conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.268042	Structured	0.408680	Uncertain	0.761	0.250	0.000							-2.662	Likely Benign	0.467	Ambiguous	Likely Benign	0.290	Likely Benign	0.1368	0.3176		0.72	Ambiguous	0.1	0.36	Likely Benign	0.54	Ambiguous	0.45	Likely Benign	-1.57	Neutral	0.000	Benign	0.001	Benign	-1.21	Pathogenic	0.09	Tolerated			2	1	2.6	-18.03
c.1431G>T	M477I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M477I is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, Rosetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Optimized all predict benign. Only FATHMM predicts pathogenic, while FoldX, Foldetta, and AlphaMissense‑Default are uncertain. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is benign, and Foldetta remains uncertain. Overall, the majority of evidence supports a benign impact, and this conclusion does not contradict the ClinVar status, which currently has no classification for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.268042	Structured	0.408680	Uncertain	0.761	0.250	0.000							-2.662	Likely Benign	0.467	Ambiguous	Likely Benign	0.291	Likely Benign	0.1368	0.3176		0.72	Ambiguous	0.1	0.36	Likely Benign	0.54	Ambiguous	0.45	Likely Benign	-1.57	Neutral	0.000	Benign	0.001	Benign	-1.21	Pathogenic	0.09	Tolerated			2	1	2.6	-18.03
c.1930G>A	D644N 2D AIThe SynGAP1 missense variant D644N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM—all classifying the substitution as benign. No tool predicts pathogenicity. The only inconclusive result is AlphaMissense‑Default, which is listed as uncertain and therefore does not influence the overall assessment. High‑accuracy methods further support a benign outcome: AlphaMissense‑Optimized predicts benign, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also reports benign. Based on the collective evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.066181	Structured	0.248888	Uncertain	0.883	0.320	0.000							-4.389	Likely Benign	0.360	Ambiguous	Likely Benign	0.124	Likely Benign	0.1368	0.6261		0.06	Likely Benign	0.3	-0.28	Likely Benign	-0.11	Likely Benign	0.02	Likely Benign	-2.28	Neutral	0.007	Benign	0.001	Benign	3.45	Benign	0.25	Tolerated			2	1	0.0	-0.98
c.2304C>A	D768E 2D AIThe SynGAP1 missense variant D768E is not reported in ClinVar and is absent from gnomAD. Consensus predictions from multiple in silico tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and FATHMM all classify the change as benign, and AlphaMissense‑Optimized also predicts a benign outcome. No tool predicts pathogenicity; AlphaMissense‑Default remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the computational evidence strongly supports a benign effect for D768E, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.332115	Structured	0.928237	Binding	0.314	0.877	0.250							-4.611	Likely Benign	0.380	Ambiguous	Likely Benign	0.065	Likely Benign	0.1368	0.7729											-1.23	Neutral	0.393	Benign	0.171	Benign	4.16	Benign	0.17	Tolerated			3	2	0.0	14.03
c.2304C>G	D768E 2D AIThe SynGAP1 missense variant D768E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus (majority vote) also indicates Likely Benign. Foldetta results are unavailable, so they do not influence the assessment. Overall, the computational evidence strongly suggests that D768E is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.332115	Structured	0.928237	Binding	0.314	0.877	0.250							-4.611	Likely Benign	0.380	Ambiguous	Likely Benign	0.065	Likely Benign	0.1368	0.7729											-1.23	Neutral	0.393	Benign	0.171	Benign	4.16	Benign	0.17	Tolerated			3	2	0.0	14.03
c.2782C>G	Q928E 2D AIThe SynGAP1 missense variant Q928E is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized predicting benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (2 vs 2) and Foldetta results are unavailable. Based on the overall distribution of predictions, the variant is most likely pathogenic; this assessment does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.497853	Structured	0.986260	Binding	0.324	0.852	0.250							-5.168	Likely Benign	0.590	Likely Pathogenic	Likely Benign	0.283	Likely Benign	0.1368	0.3477											-2.06	Neutral	0.985	Probably Damaging	0.981	Probably Damaging	1.58	Pathogenic	0.00	Affected			2	2	0.0	0.98
c.3092T>G	M1031R 2D AIThe SynGAP1 missense variant M1031R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta protein‑folding stability analysis is unavailable. Taken together, the majority of evidence points to a benign impact for M1031R, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.865454	Disordered	0.995959	Binding	0.340	0.736	0.500							-1.365	Likely Benign	0.673	Likely Pathogenic	Likely Benign	0.117	Likely Benign	0.1368	0.1212											-0.85	Neutral	0.325	Benign	0.129	Benign	2.64	Benign	0.12	Tolerated			0	-1	-6.4	24.99
c.3569G>A	S1190N 2D AIThe SynGAP1 missense variant S1190N is catalogued in gnomAD (6‑33444604‑G‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while pathogenic predictions arise from polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is uncertain, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) reports “Likely Benign,” and Foldetta results are unavailable. Overall, the balance of evidence favors a benign effect for S1190N, and this conclusion is not contradicted by any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.575842	Disordered	0.455760	Uncertain	0.742	0.624	0.625				6-33444604-G-A	2	1.24e-6	-4.909	Likely Benign	0.811	Likely Pathogenic	Ambiguous	0.326	Likely Benign	0.1368	0.3441											-1.25	Neutral	0.991	Probably Damaging	0.988	Probably Damaging	5.27	Benign	0.07	Tolerated	3.82	4	1	1	-2.7	27.03
c.1404G>A	M468I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant M468I is listed in ClinVar with an uncertain significance (ClinVar ID 3657719.0) and is present in gnomAD (6‑33438436‑G‑A). Functional prediction tools cluster into two groups: benign predictions come from premPS, PROVEAN, and SIFT, while pathogenic predictions arise from REVEL, FoldX, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, and AlphaMissense‑Default. Two tools report uncertainty: AlphaMissense‑Optimized and Rosetta. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is pathogenic. High‑accuracy assessments further support a deleterious effect: AlphaMissense‑Optimized is inconclusive, SGM Consensus is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Overall, the preponderance of evidence indicates a pathogenic impact for M468I, which does not contradict the ClinVar uncertain status but suggests a likely pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.284882	Structured	0.339253	Uncertain	0.932	0.257	0.000	Uncertain		1	6-33438436-G-A	1	6.20e-7	-8.583	Likely Pathogenic	0.907	Likely Pathogenic	Ambiguous	0.508	Likely Pathogenic	0.1369	0.3354		2.53	Destabilizing	0.2	1.89	Ambiguous	2.21	Destabilizing	0.37	Likely Benign	-1.06	Neutral	0.748	Possibly Damaging	0.886	Possibly Damaging	-1.10	Pathogenic	0.07	Tolerated	3.37	31	1	2	2.6	-18.03
c.1404G>C	M468I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M468I is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include premPS, PROVEAN, and SIFT, whereas the majority of algorithms—SGM‑Consensus, REVEL, FoldX, Foldetta, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default—classify the change as pathogenic. Two methods report uncertainty: Rosetta and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious outcome: the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenicity, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also indicates a pathogenic effect. AlphaMissense‑Optimized remains inconclusive. Overall, the preponderance of evidence points to a pathogenic impact for M468I, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.284882	Structured	0.339253	Uncertain	0.932	0.257	0.000							-8.583	Likely Pathogenic	0.907	Likely Pathogenic	Ambiguous	0.508	Likely Pathogenic	0.1369	0.3354		2.53	Destabilizing	0.2	1.89	Ambiguous	2.21	Destabilizing	0.37	Likely Benign	-1.06	Neutral	0.748	Possibly Damaging	0.886	Possibly Damaging	-1.10	Pathogenic	0.07	Tolerated	3.37	31	1	2	2.6	-18.03
c.1404G>T	M468I 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M468I is not reported in ClinVar and has no entry in gnomAD. Prediction tools that agree on a benign effect include premPS, PROVEAN, and SIFT, whereas the majority of algorithms—SGM‑Consensus, REVEL, FoldX, Foldetta, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, and AlphaMissense‑Default—classify the change as pathogenic. Two methods report uncertainty: Rosetta and AlphaMissense‑Optimized. High‑accuracy assessments further support a deleterious outcome: the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts pathogenicity, and Foldetta, which integrates FoldX‑MD and Rosetta outputs, also indicates a pathogenic effect; AlphaMissense‑Optimized remains inconclusive. Overall, the preponderance of evidence points to a pathogenic impact for M468I, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.284882	Structured	0.339253	Uncertain	0.932	0.257	0.000							-8.583	Likely Pathogenic	0.907	Likely Pathogenic	Ambiguous	0.510	Likely Pathogenic	0.1369	0.3354		2.53	Destabilizing	0.2	1.89	Ambiguous	2.21	Destabilizing	0.37	Likely Benign	-1.06	Neutral	0.748	Possibly Damaging	0.886	Possibly Damaging	-1.10	Pathogenic	0.07	Tolerated	3.37	31	1	2	2.6	-18.03
c.2465C>A	T822K 2D AIThe SynGAP1 missense variant T822K is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, and FATHMM, while polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, whereas the SGM‑Consensus remains benign; Foldetta results are unavailable. Overall, the majority of conventional tools lean toward a benign interpretation, but the high‑accuracy AlphaMissense‑Optimized prediction contradicts this. Because ClinVar has no entry for this variant, there is no existing clinical classification to conflict with; thus, the variant is most likely benign based on the preponderance of evidence, though high‑accuracy predictions remain inconclusive. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.724957	Disordered	0.651624	Binding	0.295	0.881	0.750							-1.814	Likely Benign	0.977	Likely Pathogenic	Likely Pathogenic	0.215	Likely Benign	0.1369	0.3552											-2.25	Neutral	1.000	Probably Damaging	0.988	Probably Damaging	2.51	Benign	0.07	Tolerated			0	-1	-3.2	27.07
c.2881C>T	H961Y 2D AIThe SynGAP1 missense variant H961Y is listed in ClinVar with an uncertain significance (ClinVar ID 862637.0) and is present in gnomAD (ID 6‑33443433‑C‑T). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and ESM1b. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this is not in conflict with the ClinVar uncertain status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.989835	Disordered	0.984562	Binding	0.323	0.893	0.750	Conflicting		2	6-33443433-C-T	3	1.86e-6	-8.051	Likely Pathogenic	0.157	Likely Benign	Likely Benign	0.102	Likely Benign	0.1369	0.4563											-1.07	Neutral	0.716	Possibly Damaging	0.147	Benign	4.10	Benign	0.55	Tolerated	3.77	5	0	2	1.9	26.03
c.316A>T	R106W 2D AIThe SynGAP1 missense variant R106W is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and FATHMM, while those that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. AlphaMissense‑Optimized is uncertain. High‑accuracy assessments are inconclusive: AlphaMissense‑Optimized is uncertain, the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is a 2‑vs‑2 tie, and Foldetta results are unavailable. Overall, more tools predict pathogenicity (5) than benign (3), and no ClinVar evidence contradicts this assessment. Thus, the variant is most likely pathogenic based on the available predictions. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.675549	Disordered	0.663409	Binding	0.345	0.862	0.875							-5.350	Likely Benign	0.875	Likely Pathogenic	Ambiguous	0.240	Likely Benign	0.1369	0.3995											-3.31	Deleterious	0.983	Probably Damaging	0.624	Possibly Damaging	3.62	Benign	0.00	Affected			2	-3	3.6	30.03
c.3200C>A	P1067Q 2D AIThe SynGAP1 missense variant P1067Q is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 HumDiv and SIFT predict a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign status. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign and the SGM‑Consensus is likely benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign effect for P1067Q, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.966441	Disordered	0.975099	Binding	0.459	0.907	0.875							-4.767	Likely Benign	0.114	Likely Benign	Likely Benign	0.136	Likely Benign	0.1369	0.5415											-2.39	Neutral	0.463	Possibly Damaging	0.087	Benign	2.84	Benign	0.01	Affected			0	-1	-1.9	31.01
c.3818T>G	L1273R 2D AIThe SynGAP1 missense variant L1273R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL and ESM1b, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all classify the variant as damaging. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the SGM‑Consensus outcome, the variant is most likely pathogenic; this assessment is not contradicted by any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.599170	Disordered	0.773625	Binding	0.747	0.677	0.500							-6.252	Likely Benign	0.946	Likely Pathogenic	Ambiguous	0.431	Likely Benign	0.1369	0.0761											-5.05	Deleterious	0.997	Probably Damaging	0.934	Probably Damaging	2.13	Pathogenic	0.00	Affected			-3	-2	-8.3	43.03
c.2468G>A	S823N 2D AIThe SynGAP1 missense variant S823N is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and ESM1b. Tools that agree on a pathogenic effect include polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is inconclusive (two pathogenic, two benign votes). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Based on the available predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.685117	Disordered	0.627336	Binding	0.358	0.884	0.750							-6.880	Likely Benign	0.974	Likely Pathogenic	Likely Pathogenic	0.170	Likely Benign	0.1370	0.5172											-1.76	Neutral	0.997	Probably Damaging	0.992	Probably Damaging	1.93	Pathogenic	0.00	Affected			1	1	-2.7	27.03
c.2813G>A	G938E 2D AIThe SynGAP1 missense variant G938E is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. The variant’s predicted benign status does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.905695	Disordered	0.949795	Binding	0.318	0.883	0.625							-5.394	Likely Benign	0.577	Likely Pathogenic	Likely Benign	0.112	Likely Benign	0.1370	0.3720											-1.40	Neutral	0.997	Probably Damaging	0.979	Probably Damaging	2.75	Benign	0.28	Tolerated			0	-2	-3.1	72.06
c.2984C>G	P995R 2D AIThe SynGAP1 missense variant P995R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. Only polyPhen‑2 HumDiv and SIFT predict pathogenicity. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments confirm this: AlphaMissense‑Optimized is benign and the SGM‑Consensus is Likely Benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact. The variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.862302	Disordered	0.935305	Binding	0.338	0.902	0.750							-4.605	Likely Benign	0.141	Likely Benign	Likely Benign	0.089	Likely Benign	0.1370	0.3424											-1.06	Neutral	0.586	Possibly Damaging	0.304	Benign	4.18	Benign	0.00	Affected			0	-2	-2.9	59.07
c.3251C>G	P1084R 2D AIThe SynGAP1 missense variant P1084R is not reported in ClinVar (ClinVar status: none) but is present in gnomAD (ID 6‑33443803‑C‑G). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT; AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also favors a benign outcome (2 benign vs 1 pathogenic vote). Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact for P1084R, and this conclusion does not contradict the ClinVar status, which has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.842060	Disordered	0.979020	Binding	0.348	0.889	1.000				6-33443803-C-G	4	2.52e-6	-4.171	Likely Benign	0.562	Ambiguous	Likely Benign	0.153	Likely Benign	0.1370	0.4153											-2.87	Deleterious	0.970	Probably Damaging	0.637	Possibly Damaging	3.99	Benign	0.01	Affected	3.77	5	-2	0	-2.9	59.07
c.857T>G	L286R 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant L286R is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly indicate a deleterious effect: REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as pathogenic, while Rosetta remains uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely pathogenic outcome. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts pathogenicity; the SGM‑Consensus (majority vote) is likely pathogenic; and Foldetta, which integrates FoldX‑MD (pathogenic) and Rosetta (uncertain), reports a pathogenic effect. Consequently, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar annotation, as none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.122885	Structured	0.385647	Uncertain	0.932	0.260	0.000							-15.563	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.868	Likely Pathogenic	0.1370	0.0600		2.90	Destabilizing	0.3	1.80	Ambiguous	2.35	Destabilizing	1.97	Destabilizing	-5.52	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	1.49	Pathogenic	0.00	Affected			-3	-2	-8.3	43.03
c.1229G>C	S410T 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S410T has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include AlphaMissense‑Default, AlphaMissense‑Optimized, ESM1b, FATHMM, PROVEAN, FoldX, Foldetta, SGM‑Consensus, REVEL, polyPhen‑2 (HumDiv and HumVar), SIFT, and premPS. No tool predicts a pathogenic outcome; the only inconclusive result is from Rosetta, which is treated as unavailable. High‑accuracy assessments are consistent: AlphaMissense‑Optimized predicts benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates likely benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts benign. **Thus, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is available).** Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.098513	Structured	0.349627	Uncertain	0.908	0.206	0.000							-6.559	Likely Benign	0.123	Likely Benign	Likely Benign	0.066	Likely Benign	0.1371	0.7159		-0.32	Likely Benign	0.1	-0.52	Ambiguous	-0.42	Likely Benign	0.00	Likely Benign	-0.78	Neutral	0.080	Benign	0.026	Benign	4.24	Benign	0.84	Tolerated			1	1	0.1	14.03
c.2365C>A	P789T 2D AIThe SynGAP1 P789T missense variant has no ClinVar entry and is not present in gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and AlphaMissense‑Optimized, while pathogenic predictions arise from PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and FATHMM. AlphaMissense‑Default remains uncertain. High‑accuracy assessments further clarify the variant’s likely effect: AlphaMissense‑Optimized predicts a benign outcome, whereas the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—leans pathogenic (2 pathogenic vs. 1 benign). Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, did not provide a result for this variant, so its status is unavailable. Overall, the preponderance of evidence from both general and high‑accuracy tools indicates that P789T is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is reported. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.963420	Disordered	0.541575	Binding	0.398	0.903	0.750							-5.242	Likely Benign	0.356	Ambiguous	Likely Benign	0.224	Likely Benign	0.1371	0.3837											-4.77	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.06	Pathogenic	0.00	Affected			0	-1	0.9	3.99
c.1406C>A	A469D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A469D is listed in ClinVar with an uncertain significance and is not reported in gnomAD. Prediction tools that assess the variant’s effect fall into two groups: the single benign prediction from SIFT, and a consensus of pathogenic predictions from the remaining 15 tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus). High‑accuracy methods further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) also indicates pathogenic. Taken together, the overwhelming majority of evidence points to a pathogenic effect, which is consistent with the ClinVar uncertain status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.278302	Structured	0.343926	Uncertain	0.910	0.276	0.000	Uncertain		1				-14.643	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.738	Likely Pathogenic	0.1372	0.1583		5.09	Destabilizing	0.2	4.16	Destabilizing	4.63	Destabilizing	1.68	Destabilizing	-3.48	Deleterious	0.999	Probably Damaging	0.996	Probably Damaging	-1.34	Pathogenic	0.21	Tolerated	3.37	34	0	-2	-5.3	44.01	237.0	-58.2	-0.2	0.1	0.8	0.1	X		X					Potentially Pathogenic	The methyl group of Ala469, located in an α helix (res. Ala461–Phe476), interacts with hydrophobic residues (e.g., Trp572, Leu588, Met470) in an inter-helix space formed by two other α helices (res. Glu582–Ser604, res. Arg563–Gly580). In the variant simulations, Asp469 introduces a negatively charged and bulky side chain into the hydrophobic niche. Consequently, the side chain of Asp469 rotates outward, allowing the carboxylate group to form a salt bridge with the guanidinium group of Arg575 on the protein surface. This interaction affects the continuity of the parent α helix (Ala461–Phe476). Due to the importance of hydrophobic packing, the structural effects could be more pronounced during actual protein folding.
c.2222C>A	P741H 2D AIThe SynGAP1 missense variant P741H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus from SGM (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) classifies the variant as Likely Benign, and AlphaMissense‑Optimized also predicts Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect. The prediction is consistent with the lack of ClinVar annotation, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.885302	Disordered	0.493550	Uncertain	0.354	0.859	0.875							-5.592	Likely Benign	0.085	Likely Benign	Likely Benign	0.099	Likely Benign	0.1372	0.3831											-0.99	Neutral	0.006	Benign	0.007	Benign	2.81	Benign	0.01	Affected			0	-2	-1.6	40.02
c.2414T>G	L805R 2D AIThe SynGAP1 missense variant L805R is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. In contrast, the majority of tools predict a pathogenic impact: SGM‑Consensus, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default all indicate pathogenicity. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as benign, whereas the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) labels it as likely pathogenic; Foldetta results are unavailable. Overall, the balance of evidence from the broader set of predictors leans toward pathogenicity, and this conclusion does not contradict any existing ClinVar annotation, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	SH3-binding motif	0.775545	Disordered	0.827669	Binding	0.341	0.903	0.625							-6.640	Likely Benign	0.569	Likely Pathogenic	Likely Benign	0.196	Likely Benign	0.1372	0.0908											-3.00	Deleterious	0.927	Possibly Damaging	0.617	Possibly Damaging	2.37	Pathogenic	0.00	Affected			-3	-2	-8.3	43.03
c.712G>C	E238Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E238Q missense variant has no ClinVar entry and is not reported in gnomAD. Prediction tools cluster into two consensus groups: benign predictions come from SIFT and FATHMM, while pathogenic predictions are made by REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score (Likely Pathogenic). Stability‑based methods (FoldX, Rosetta, premPS) and Foldetta give uncertain or inconclusive results and are treated as unavailable. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts Pathogenic, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Pathogenic, while Foldetta remains uncertain. Overall, the majority of evidence points to a pathogenic effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.194234	Structured	0.332638	Uncertain	0.796	0.326	0.000							-11.476	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	0.723	Likely Pathogenic	0.1372	0.5412		0.63	Ambiguous	0.5	0.59	Ambiguous	0.61	Ambiguous	0.52	Ambiguous	-2.72	Deleterious	0.996	Probably Damaging	0.891	Possibly Damaging	5.44	Benign	0.06	Tolerated			2	2	0.0	-0.98
c.1694T>G	L565R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L565R is not reported in ClinVar (ClinVar status: not listed) but is present in the gnomAD database (gnomAD ID: 6‑33440746‑T‑G). Prediction tools that agree on a benign effect include only FATHMM, whereas the remaining tools—REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, Foldetta, and the SGM Consensus—consistently predict a pathogenic impact. The Rosetta stability assessment is inconclusive and is therefore treated as unavailable. High‑accuracy methods all support pathogenicity: AlphaMissense‑Optimized is pathogenic, the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is pathogenic. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar evidence (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.034884	Structured	0.045819	Uncertain	0.922	0.205	0.000				6-33440746-T-G			-16.070	Likely Pathogenic	0.998	Likely Pathogenic	Likely Pathogenic	0.547	Likely Pathogenic	0.1373	0.0615		4.71	Destabilizing	0.1	1.88	Ambiguous	3.30	Destabilizing	2.66	Destabilizing	-5.97	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	2.74	Benign	0.00	Affected	3.37	35	-2	-3	-8.3	43.03
c.2360C>G	P787R 2D AIThe SynGAP1 missense variant P787R is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, FATHMM, and AlphaMissense‑Optimized, while those that predict a pathogenic effect are PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive due to a 2‑vs‑2 split, and Foldetta results are unavailable. Overall, the majority of conventional tools lean toward pathogenicity, whereas the single high‑accuracy tool indicates benign and the consensus is unresolved. Thus, the variant is most likely pathogenic based on the prevailing predictions, and this assessment does not contradict ClinVar status, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		SH3-binding motif	0.901269	Disordered	0.613211	Binding	0.377	0.899	0.750							-5.013	Likely Benign	0.784	Likely Pathogenic	Likely Benign	0.268	Likely Benign	0.1373	0.2741											-4.41	Deleterious	1.000	Probably Damaging	0.999	Probably Damaging	2.50	Benign	0.03	Affected			0	-2	-2.9	59.07
c.3800T>A	M1267K 2D AIThe SynGAP1 missense variant M1267K is not reported in ClinVar and has no entries in gnomAD. Functional prediction tools show a split: benign calls come from REVEL and ESM1b, while pathogenic calls are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, and AlphaMissense‑Default. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, favors a pathogenic outcome (3/4 pathogenic). AlphaMissense‑Optimized is uncertain, and no Foldetta stability assessment is available. Overall, the majority of evidence points to a deleterious effect, classifying the variant as most likely pathogenic. This assessment does not conflict with ClinVar, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.429200	Structured	0.812047	Binding	0.847	0.614	0.000							-6.415	Likely Benign	0.917	Likely Pathogenic	Ambiguous	0.366	Likely Benign	0.1373	0.0488											-5.01	Deleterious	0.884	Possibly Damaging	0.581	Possibly Damaging	2.31	Pathogenic	0.00	Affected			0	-1	-5.8	-3.02
c.521T>A	M174K 2D AIThe SynGAP1 missense variant M174K has no ClinVar entry and is not reported in gnomAD. Prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and FATHMM. Tools that predict a pathogenic effect are PROVEAN, SIFT, ESM1b, and AlphaMissense‑Default. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic, and AlphaMissense‑Optimized independently predicts it as Pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence from high‑accuracy predictors and the consensus score points to a pathogenic classification. This assessment is not contradicted by ClinVar, which currently contains no entry for M174K. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.661982	Disordered	0.485854	Uncertain	0.373	0.620	0.375							-9.542	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.325	Likely Benign	0.1373	0.0688											-3.21	Deleterious	0.002	Benign	0.002	Benign	4.06	Benign	0.01	Affected			0	-1	-5.8	-3.02
c.1644G>C	E548D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E548D variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Functional prediction tools that agree on a benign effect include REVEL, premPS, SIFT, and FATHMM, whereas a separate group predicts pathogenicity: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. Predictions that are uncertain or unavailable are FoldX, Rosetta, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a pathogenic verdict (2 pathogenic, 1 benign, 1 uncertain). Foldetta’s stability prediction is unavailable. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict the ClinVar status, which simply lacks an entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.054297	Structured	0.008632	Uncertain	0.965	0.288	0.000							-7.359	In-Between	0.992	Likely Pathogenic	Likely Pathogenic	0.254	Likely Benign	0.1374	0.2524		0.74	Ambiguous	0.1	1.29	Ambiguous	1.02	Ambiguous	0.32	Likely Benign	-2.85	Deleterious	0.998	Probably Damaging	0.989	Probably Damaging	3.51	Benign	0.09	Tolerated			3	2	0.0	-14.03
c.1644G>T	E548D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 E548D variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Functional prediction tools that agree on a benign effect include REVEL, premPS, SIFT, and FATHMM, whereas a separate group predicts a pathogenic effect: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. Predictions that are uncertain or unavailable are FoldX, Rosetta, Foldetta, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic; the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a pathogenic verdict (2 pathogenic, 1 benign, 1 uncertain). Foldetta’s stability prediction is unavailable. Overall, the majority of evidence points to a pathogenic impact for E548D, and this conclusion does not contradict the lack of ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.054297	Structured	0.008632	Uncertain	0.965	0.288	0.000							-7.359	In-Between	0.992	Likely Pathogenic	Likely Pathogenic	0.254	Likely Benign	0.1374	0.2524		0.74	Ambiguous	0.1	1.29	Ambiguous	1.02	Ambiguous	0.32	Likely Benign	-2.85	Deleterious	0.998	Probably Damaging	0.989	Probably Damaging	3.51	Benign	0.09	Tolerated			3	2	0.0	-14.03
c.2174T>G	L725R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L725R is not reported in ClinVar (ClinVar ID = None) and is absent from gnomAD (gnomAD ID = None). Prediction tools that agree on a benign effect include only REVEL, which scores the variant as benign. All other evaluated algorithms—polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, PROVEAN, AlphaMissense‑Default, AlphaMissense‑Optimized, premPS, Rosetta, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN)—classify the variant as pathogenic. FoldX and Foldetta report uncertain results and are therefore not considered evidence for either side. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM‑Consensus indicates likely pathogenic, while Foldetta remains uncertain. Based on the overwhelming majority of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, which is consistent with the absence of a ClinVar entry and gnomAD observation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.557691	Disordered	0.455613	Uncertain	0.911	0.491	0.625							-15.383	Likely Pathogenic	0.961	Likely Pathogenic	Likely Pathogenic	0.345	Likely Benign	0.1374	0.0846		0.69	Ambiguous	0.3	2.16	Destabilizing	1.43	Ambiguous	1.49	Destabilizing	-5.46	Deleterious	0.999	Probably Damaging	0.998	Probably Damaging	1.28	Pathogenic	0.00	Affected			-3	-2	-8.3	43.03
c.2029A>T	S677C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S677C is reported in ClinVar as Benign (ClinVar ID 2825814.0) and is not present in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, premPS, PROVEAN, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, polyPhen‑2 HumVar, and the SGM‑Consensus (Likely Benign). In contrast, polyPhen‑2 HumDiv, SIFT, and ESM1b predict a pathogenic impact. High‑accuracy predictors all support a benign outcome: AlphaMissense‑Optimized is benign, the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) is benign. No prediction or folding‑stability result is missing or inconclusive. Based on the preponderance of evidence, the variant is most likely benign, and this assessment aligns with its ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.194234	Structured	0.115685	Uncertain	0.555	0.338	0.125	Benign		1				-8.496	Likely Pathogenic	0.076	Likely Benign	Likely Benign	0.153	Likely Benign	0.1375	0.6697		-0.51	Ambiguous	0.3	-0.30	Likely Benign	-0.41	Likely Benign	0.15	Likely Benign	-2.41	Neutral	0.932	Possibly Damaging	0.222	Benign	3.25	Benign	0.04	Affected	3.41	23	-1	0	3.3	16.06
c.2119G>C	A707P 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant A707P is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL, FoldX, SIFT, and FATHMM, whereas pathogenic predictions come from Foldetta, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, and AlphaMissense‑Default. Two tools give uncertain results: AlphaMissense‑Optimized and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as uncertain, SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) as Likely Pathogenic, and Foldetta (combining FoldX‑MD and Rosetta) as Pathogenic. Overall, the majority of evidence points to a pathogenic effect, and this assessment does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.203355	Structured	0.371229	Uncertain	0.927	0.365	0.000							-8.082	Likely Pathogenic	0.885	Likely Pathogenic	Ambiguous	0.228	Likely Benign	0.1375	0.3095		0.28	Likely Benign	0.1	5.75	Destabilizing	3.02	Destabilizing	0.76	Ambiguous	-2.92	Deleterious	0.996	Probably Damaging	0.983	Probably Damaging	3.41	Benign	0.09	Tolerated			1	-1	-3.4	26.04
c.2204G>A	S735N 2D AIThe SynGAP1 missense variant S735N is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. No pathogenic predictions are present among the evaluated tools. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.916840	Disordered	0.412174	Uncertain	0.290	0.752	0.875							-6.697	Likely Benign	0.142	Likely Benign	Likely Benign	0.068	Likely Benign	0.1375	0.3827											-0.68	Neutral	0.400	Benign	0.138	Benign	2.65	Benign	0.18	Tolerated			1	1	-2.7	27.03
c.1651C>G	L551V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L551V is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include PROVEAN, SIFT, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are REVEL, FoldX, premPS, polyPhen‑2 (HumDiv and HumVar), ESM1b, and FATHMM. Two tools give uncertain results: AlphaMissense‑Default and Foldetta. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is pathogenic. Foldetta’s stability prediction is uncertain. Overall, the majority of evidence points to a pathogenic impact for L551V. This conclusion does not contradict ClinVar status, as the variant is currently unreported in that database. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.009977	Structured	0.006653	Uncertain	0.960	0.254	0.000							-10.154	Likely Pathogenic	0.556	Ambiguous	Likely Benign	0.575	Likely Pathogenic	0.1376	0.2778		2.04	Destabilizing	0.0	1.41	Ambiguous	1.73	Ambiguous	1.03	Destabilizing	-1.39	Neutral	0.998	Probably Damaging	0.992	Probably Damaging	-1.48	Pathogenic	0.22	Tolerated			2	1	0.4	-14.03
c.2120C>A	A707D 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant A707D is not reported in ClinVar (status: None) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, FoldX, FATHMM, AlphaMissense‑Optimized, and Foldetta. Tools that predict a pathogenic effect are SGM‑Consensus, AlphaMissense‑Default, ESM1b, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. Two tools give uncertain results: premPS and Rosetta. High‑accuracy methods give a mixed picture: AlphaMissense‑Optimized predicts benign, SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts likely pathogenic, and Foldetta predicts benign. Overall, the majority of evidence points to a pathogenic impact, and this assessment does not contradict any ClinVar classification because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.203355	Structured	0.371229	Uncertain	0.927	0.365	0.000							-9.160	Likely Pathogenic	0.772	Likely Pathogenic	Likely Benign	0.225	Likely Benign	0.1376	0.1741		0.29	Likely Benign	0.0	-0.61	Ambiguous	-0.16	Likely Benign	0.89	Ambiguous	-3.16	Deleterious	0.996	Probably Damaging	0.983	Probably Damaging	3.39	Benign	0.02	Affected			0	-2	-5.3	44.01
c.2539C>G	Q847E 2D AIThe SynGAP1 missense variant Q847E is not reported in ClinVar (ClinVar status: not reported) and is absent from gnomAD (gnomAD: not present). Prediction tools that agree on a benign effect include REVEL, PROVEAN, and AlphaMissense‑Optimized. Those that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. Two tools remain uncertain: AlphaMissense‑Default and ESM1b. High‑accuracy assessment shows AlphaMissense‑Optimized predicts a benign outcome, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a tie between benign and pathogenic signals; Foldetta’s protein‑folding stability analysis is unavailable. Overall, the majority of conventional predictors lean toward pathogenicity, whereas the single high‑accuracy tool suggests benign. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.653063	Disordered	0.577677	Binding	0.282	0.818	0.500							-7.864	In-Between	0.377	Ambiguous	Likely Benign	0.140	Likely Benign	0.1376	0.2083											-2.12	Neutral	0.649	Possibly Damaging	0.535	Possibly Damaging	2.31	Pathogenic	0.00	Affected			2	2	0.0	0.98
c.3146C>G	P1049R 2D AIThe SynGAP1 missense variant P1049R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.978316	Disordered	0.917915	Binding	0.428	0.920	0.750							-5.144	Likely Benign	0.145	Likely Benign	Likely Benign	0.067	Likely Benign	0.1376	0.3769											-1.90	Neutral	0.791	Possibly Damaging	0.500	Possibly Damaging	2.74	Benign	0.03	Affected			0	-2	-2.9	59.07
c.358G>T	G120C 2D AIThe SynGAP1 missense variant G120C is not reported in ClinVar and is absent from gnomAD, indicating no documented allele frequency data. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict a benign effect. No tool in the dataset indicates pathogenicity. High‑accuracy assessments corroborate this benign prediction: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) yields a “Likely Benign” classification. Foldetta results are not available, so they do not influence the assessment. Overall, the variant is most likely benign, and this conclusion is consistent with the absence of any ClinVar pathogenic annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.707965	Disordered	0.659993	Binding	0.359	0.887	0.750							-5.979	Likely Benign	0.179	Likely Benign	Likely Benign	0.041	Likely Benign	0.1376	0.4225											-0.73	Neutral	0.410	Benign	0.146	Benign	4.20	Benign	0.10	Tolerated			-3	-3	2.9	46.09
c.4003G>T	G1335C 2D AIThe SynGAP1 missense variant G1335C is listed in gnomAD (variant ID 6-33451877‑G‑T) but has no ClinVar entry. Functional prediction tools split into two groups: benign predictions come from REVEL and ESM1b, while pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, and the SGM‑Consensus (majority vote) also indicates Likely Pathogenic. Foldetta results are not available for this variant. Overall, the majority of evidence points to a pathogenic effect, and this conclusion does not contradict any ClinVar status, as no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.891961	Disordered	0.967705	Binding	0.323	0.724	0.750				6-33451877-G-T	1	7.91e-7	-6.878	Likely Benign	0.997	Likely Pathogenic	Likely Pathogenic	0.426	Likely Benign	0.1376	0.4513											-5.51	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	2.01	Pathogenic	0.00	Affected	3.77	5	-3	-3	2.9	46.09
c.1291C>G	L431V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 L431V missense variant is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, SIFT, FATHMM, AlphaMissense‑Optimized, and polyPhen‑2 HumVar. Those that predict a pathogenic effect are FoldX, premPS, PROVEAN, and polyPhen‑2 HumDiv. Four tools (Rosetta, Foldetta, ESM1b, AlphaMissense‑Default) give uncertain or inconclusive results. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive due to a 1‑to‑1 split between benign and pathogenic signals, and Foldetta also yields an uncertain outcome. Overall, the balance of evidence—including the higher number of benign predictions and the benign call from the most accurate tool—suggests that the variant is most likely benign. This conclusion does not contradict the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.094817	Structured	0.374755	Uncertain	0.959	0.300	0.000							-7.949	In-Between	0.505	Ambiguous	Likely Benign	0.093	Likely Benign	0.1377	0.3198		2.17	Destabilizing	0.0	1.50	Ambiguous	1.84	Ambiguous	1.32	Destabilizing	-2.58	Deleterious	0.861	Possibly Damaging	0.332	Benign	3.04	Benign	0.20	Tolerated			2	1	0.4	-14.03
c.160A>C	N54H 2D AISynGAP1 missense variant N54H is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, and SIFT. ESM1b is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the preponderance of evidence points to a benign impact for the variant, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.196879	Structured	0.464669	Uncertain	0.504	0.659	0.000							-7.646	In-Between	0.236	Likely Benign	Likely Benign	0.112	Likely Benign	0.1377	0.7334											-1.18	Neutral	0.943	Possibly Damaging	0.924	Probably Damaging	4.14	Benign	0.00	Affected			2	1	0.3	23.04
c.3086A>G	Q1029R 2D AIThe SynGAP1 missense variant Q1029R has no ClinVar entry and is not reported in gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (both HumDiv and HumVar) predict a pathogenic outcome. AlphaMissense‑Default remains uncertain, and the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates likely benign; Foldetta results are unavailable. Based on the preponderance of evidence from both general and high‑accuracy predictors, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.852992	Disordered	0.995643	Binding	0.375	0.734	0.500							-3.437	Likely Benign	0.420	Ambiguous	Likely Benign	0.073	Likely Benign	0.1377	0.2420											-0.72	Neutral	0.961	Probably Damaging	0.677	Possibly Damaging	2.73	Benign	0.88	Tolerated			1	1	-1.0	28.06
c.343C>G	Q115E 2D AIThe SynGAP1 missense variant Q115E is reported in gnomAD (variant ID 6‑33432208‑C‑G) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. In contrast, polyPhen‑2 (both HumDiv and HumVar models) predict a pathogenic impact. When predictions are grouped by consensus, the benign group contains seven tools, whereas the pathogenic group contains two. High‑accuracy assessments reinforce the benign view: AlphaMissense‑Optimized reports a benign outcome, and the SGM‑Consensus (derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates a likely benign effect. No Foldetta stability analysis is available, so it does not influence the overall assessment. Based on the preponderance of evidence, the variant is most likely benign, and this conclusion does not contradict any ClinVar status (none is assigned). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.784345	Disordered	0.657256	Binding	0.327	0.878	0.750				6-33432208-C-G	1	6.20e-7	-3.465	Likely Benign	0.229	Likely Benign	Likely Benign	0.096	Likely Benign	0.1377	0.1832											-0.40	Neutral	0.924	Possibly Damaging	0.857	Possibly Damaging	4.18	Benign	0.42	Tolerated	3.61	5	2	2	0.0	0.98
c.3848C>G	P1283R 2D AIThe SynGAP1 missense variant P1283R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote) which classifies the variant as Likely Benign. In contrast, polyPhen‑2 (HumDiv and HumVar) and SIFT all predict a pathogenic impact. High‑accuracy assessments further support a benign outcome: AlphaMissense‑Optimized returns Benign, and the SGM‑Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also indicates Likely Benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign effect, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.762850	Disordered	0.819686	Binding	0.484	0.732	0.875							-3.643	Likely Benign	0.130	Likely Benign	Likely Benign	0.067	Likely Benign	0.1377	0.2211											-1.40	Neutral	0.911	Possibly Damaging	0.567	Possibly Damaging	2.72	Benign	0.05	Affected			0	-2	-2.9	59.07
c.1687A>T	R563W 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R563W is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, premPS, and FATHMM, whereas a majority of tools (SGM‑Consensus, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, and AlphaMissense‑Default) predict a pathogenic impact. High‑accuracy assessments show that AlphaMissense‑Optimized is inconclusive, the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. No evidence from the uncertain tools (FoldX, Rosetta, Foldetta, AlphaMissense‑Optimized) supports either outcome. Overall, the balance of evidence favors a pathogenic classification for R563W, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.039760	Structured	0.031987	Uncertain	0.876	0.209	0.000							-12.454	Likely Pathogenic	0.854	Likely Pathogenic	Ambiguous	0.302	Likely Benign	0.1378	0.2088		1.25	Ambiguous	0.1	0.79	Ambiguous	1.02	Ambiguous	0.34	Likely Benign	-6.75	Deleterious	1.000	Probably Damaging	0.997	Probably Damaging	3.42	Benign	0.01	Affected			2	-3	3.6	30.03
c.925G>T	G309C 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant G309C is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a deleterious effect include REVEL, FoldX, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus score, all of which classify the change as pathogenic or likely pathogenic. Tools with inconclusive results—Rosetta, Foldetta, and premPS—return uncertain outcomes and do not alter the overall assessment. High‑accuracy methods further support a damaging effect: AlphaMissense‑Optimized predicts pathogenic, the SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates likely pathogenic, whereas Foldetta’s stability analysis is inconclusive. Taken together, the evidence strongly favors a pathogenic interpretation, and this conclusion is consistent with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.275179	Structured	0.338439	Uncertain	0.882	0.342	0.125							-14.331	Likely Pathogenic	0.999	Likely Pathogenic	Likely Pathogenic	0.656	Likely Pathogenic	0.1378	0.4574		2.60	Destabilizing	0.4	1.09	Ambiguous	1.85	Ambiguous	0.67	Ambiguous	-8.27	Deleterious	1.000	Probably Damaging	1.000	Probably Damaging	1.66	Pathogenic	0.00	Affected			-3	-3	2.9	46.09
c.1706T>A	F569Y 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 F569Y missense variant is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include only SIFT, whereas the majority of tools (REVEL, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default) predict a pathogenic impact. FoldX, Rosetta, Foldetta, and AlphaMissense‑Optimized are inconclusive, providing no definitive evidence for either outcome. High‑accuracy assessments show that the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) strongly supports pathogenicity, while AlphaMissense‑Optimized remains uncertain and Foldetta likewise yields an inconclusive result. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict the current ClinVar status, which contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.024393	Structured	0.054289	Uncertain	0.941	0.242	0.000							-11.101	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	0.824	Likely Pathogenic	0.1379	0.1170		1.57	Ambiguous	0.1	0.82	Ambiguous	1.20	Ambiguous	1.29	Destabilizing	-2.99	Deleterious	0.993	Probably Damaging	0.976	Probably Damaging	-1.37	Pathogenic	0.08	Tolerated			7	3	-4.1	16.00
c.1836G>C	Q612H 2D AIThe SynGAP1 missense variant Q612H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are limited to Rosetta, which scores the variant as benign. All other evaluated predictors—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM Consensus confirms a likely pathogenic status, while Foldetta (combining FoldX‑MD and Rosetta outputs) remains uncertain. FoldX and premPS are inconclusive, and Foldetta is unavailable for definitive interpretation. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.275179	Structured	0.203988	Uncertain	0.822	0.263	0.000							-9.733	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	0.550	Likely Pathogenic	0.1379	0.3084		0.70	Ambiguous	0.9	0.39	Likely Benign	0.55	Ambiguous	0.79	Ambiguous	-4.55	Deleterious	0.991	Probably Damaging	0.986	Probably Damaging	-1.26	Pathogenic	0.02	Affected			3	0	0.3	9.01
c.1836G>T	Q612H 2D AIThe SynGAP1 missense variant Q612H is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect are limited to Rosetta, which scores the variant as benign. All other evaluated predictors—REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. The SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely pathogenic outcome. High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized predicts pathogenic, SGM Consensus confirms a likely pathogenic status, while Foldetta (combining FoldX‑MD and Rosetta outputs) remains uncertain. FoldX and premPS are inconclusive, and Foldetta is unavailable for definitive interpretation. Based on the collective predictions, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status, as none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.275179	Structured	0.203988	Uncertain	0.822	0.263	0.000							-9.733	Likely Pathogenic	0.956	Likely Pathogenic	Likely Pathogenic	0.550	Likely Pathogenic	0.1379	0.3084		0.70	Ambiguous	0.9	0.39	Likely Benign	0.55	Ambiguous	0.79	Ambiguous	-4.55	Deleterious	0.991	Probably Damaging	0.986	Probably Damaging	-1.26	Pathogenic	0.02	Affected			3	0	0.3	9.01
c.2915C>G	P972R 2D AIThe SynGAP1 missense variant P972R is reported in gnomAD (ID 6‑33443467‑C‑G) but has no ClinVar entry. All evaluated in silico predictors classify it as benign: REVEL, PROVEAN, PolyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta results are unavailable. Based on the unanimous benign predictions and lack of ClinVar pathogenic annotation, the variant is most likely benign and does not contradict ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.891961	Disordered	0.954150	Binding	0.472	0.904	0.625				6-33443467-C-G			-4.483	Likely Benign	0.139	Likely Benign	Likely Benign	0.043	Likely Benign	0.1379	0.3931											-1.44	Neutral	0.290	Benign	0.114	Benign	4.23	Benign	0.12	Tolerated	4.32	2	-2	0	-2.9	59.07
c.2924C>A	T975N 2D AIThe SynGAP1 missense variant T975N is listed in ClinVar (ID 942242.0) with an “Uncertain” clinical significance and is present in gnomAD (variant ID 6‑33443476‑C‑A). Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all report benign or tolerated outcomes. Only polyPhen‑2 HumDiv predicts a pathogenic effect. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as “Likely Benign.” High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, which is consistent with the ClinVar “Uncertain” status rather than contradicting it. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.871313	Disordered	0.969331	Binding	0.332	0.890	0.625	Uncertain		1	6-33443476-C-A	1	6.20e-7	-4.671	Likely Benign	0.089	Likely Benign	Likely Benign	0.100	Likely Benign	0.1379	0.4772											-0.58	Neutral	0.586	Possibly Damaging	0.302	Benign	4.13	Benign	0.07	Tolerated	4.32	2	0	0	-2.8	13.00
c.3097T>A	S1033T 2D AIThe SynGAP1 missense variant S1033T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only polyPhen‑2 HumDiv predicts a pathogenic outcome. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus also indicates Likely Benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence points to a benign effect, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.910643	Disordered	0.993473	Binding	0.294	0.737	0.625							-3.702	Likely Benign	0.140	Likely Benign	Likely Benign	0.029	Likely Benign	0.1379	0.6089											-0.05	Neutral	0.568	Possibly Damaging	0.171	Benign	2.73	Benign	0.58	Tolerated			1	1	0.1	14.03
c.147C>G	C49W 2D AIThe SynGAP1 missense variant C49W is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL and FATHMM, whereas the majority of tools predict a pathogenic impact: PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic and the SGM‑Consensus is “Likely Pathogenic.” Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy predictors indicates that C49W is most likely pathogenic, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.209395	Structured	0.445316	Uncertain	0.541	0.704	0.000							-12.247	Likely Pathogenic	0.977	Likely Pathogenic	Likely Pathogenic	0.291	Likely Benign	0.1380	0.3172											-3.56	Deleterious	0.880	Possibly Damaging	0.914	Probably Damaging	3.83	Benign	0.00	Affected			-8	-2	-3.4	83.07
c.163C>G	Q55E 2D AIThe SynGAP1 missense variant Q55E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign, while SIFT uniquely predicts pathogenic. ESM1b is uncertain. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as likely benign. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized predicts benign and the SGM‑Consensus also indicates likely benign; Foldetta results are unavailable. Overall, the consensus of the available predictions points to a benign impact, and this is consistent with the lack of ClinVar evidence; there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.332115	Structured	0.470108	Uncertain	0.461	0.657	0.000							-7.361	In-Between	0.265	Likely Benign	Likely Benign	0.052	Likely Benign	0.1380	0.2632											-0.98	Neutral	0.064	Benign	0.184	Benign	3.89	Benign	0.00	Affected			2	2	0.0	0.98
c.2077C>A	H693N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant H693N is not reported in ClinVar and is absent from gnomAD. Prediction tools that classify it as benign include REVEL and FATHMM, whereas the majority of other in silico predictors—premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM Consensus—label it pathogenic. FoldX, Rosetta, and Foldetta provide uncertain results. High‑accuracy methods specifically give AlphaMissense‑Optimized as pathogenic, the SGM Consensus as likely pathogenic, and Foldetta as uncertain. Overall, the preponderance of evidence points to a pathogenic effect for H693N, and this assessment does not contradict the absence of a ClinVar entry. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.073402	Structured	0.323991	Uncertain	0.964	0.260	0.000							-12.275	Likely Pathogenic	0.978	Likely Pathogenic	Likely Pathogenic	0.436	Likely Benign	0.1380	0.1849		1.74	Ambiguous	0.1	0.80	Ambiguous	1.27	Ambiguous	1.28	Destabilizing	-6.98	Deleterious	1.000	Probably Damaging	0.987	Probably Damaging	3.10	Benign	0.01	Affected			2	1	-0.3	-23.04
c.2626T>A	S876T 2D AIThe SynGAP1 missense variant S876T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. The only tools that predict a pathogenic outcome are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are not available. Based on the preponderance of evidence, the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.549308	Disordered	0.631130	Binding	0.280	0.872	0.250							-5.158	Likely Benign	0.183	Likely Benign	Likely Benign	0.121	Likely Benign	0.1380	0.6790											-1.91	Neutral	0.979	Probably Damaging	0.982	Probably Damaging	2.60	Benign	0.11	Tolerated			1	1	0.1	14.03
c.2948G>T	S983I 2D AIThe SynGAP1 missense variant S983I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). In silico predictors that agree on a benign effect are REVEL and ESM1b, whereas the majority of tools predict a pathogenic outcome: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). High‑accuracy assessments further support pathogenicity: AlphaMissense‑Optimized is pathogenic, and the SGM‑Consensus (3 pathogenic vs. 1 benign) is likely pathogenic. Foldetta results are unavailable. Overall, the preponderance of evidence indicates that S983I is most likely pathogenic, and this conclusion is not contradicted by the current ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.707965	Disordered	0.960212	Binding	0.277	0.889	0.625							-6.259	Likely Benign	0.968	Likely Pathogenic	Likely Pathogenic	0.190	Likely Benign	0.1380	0.4625											-2.67	Deleterious	0.997	Probably Damaging	0.996	Probably Damaging	2.02	Pathogenic	0.00	Affected			-1	-2	5.3	26.08
c.3316C>G	Q1106E 2D AIThe SynGAP1 missense variant Q1106E is not reported in ClinVar and has no entry in gnomAD. Functional prediction tools largely agree on a benign effect: SGM‑Consensus (Likely Benign), REVEL, PROVEAN, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized all predict benign. In contrast, PolyPhen‑2 (HumDiv and HumVar) and FATHMM predict pathogenicity. High‑accuracy assessments reinforce the benign consensus: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is also likely benign. No Foldetta stability prediction is available, so it does not influence the assessment. Overall, the majority of evidence points to a benign impact for Q1106E, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.885302	Disordered	0.952043	Binding	0.382	0.870	0.875							-5.074	Likely Benign	0.307	Likely Benign	Likely Benign	0.127	Likely Benign	0.1381	0.2663											-1.60	Neutral	0.963	Probably Damaging	0.959	Probably Damaging	1.80	Pathogenic	0.15	Tolerated			2	2	0.0	0.98
c.3365G>T	G1122V 2D AIThe SynGAP1 missense variant G1122V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools uniformly classify the variant as benign: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all return benign scores. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. No tool predicts pathogenicity. High‑accuracy assessments corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) reports likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign, and this assessment is consistent with the absence of a ClinVar pathogenic classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.896620	Disordered	0.814918	Binding	0.357	0.932	0.875							-6.398	Likely Benign	0.088	Likely Benign	Likely Benign	0.271	Likely Benign	0.1381	0.3694											-1.18	Neutral	0.059	Benign	0.025	Benign	4.49	Benign	0.10	Tolerated			-1	-3	4.6	42.08
c.3667C>G	L1223V 2D AIThe SynGAP1 missense variant L1223V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show mixed results: benign predictions come from REVEL, PROVEAN, and AlphaMissense‑Optimized, whereas pathogenic predictions are made by polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, is classified as Likely Pathogenic, reflecting a majority of pathogenic calls. High‑accuracy assessments further support this: AlphaMissense‑Optimized predicts benign, while the SGM‑Consensus (majority vote) predicts pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the balance of evidence leans toward pathogenicity, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.608892	Disordered	0.436267	Uncertain	0.868	0.540	0.375							-8.492	Likely Pathogenic	0.678	Likely Pathogenic	Likely Benign	0.178	Likely Benign	0.1381	0.2988											-2.18	Neutral	0.981	Probably Damaging	0.832	Possibly Damaging	1.54	Pathogenic	0.04	Affected			2	1	0.4	-14.03
c.655T>C	C219R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant C219R is not reported in ClinVar (ClinVar ID None) and has no entries in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include only FATHMM, while the remaining 13 tools—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic or likely pathogenic impact. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized reports Pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) indicates Likely Pathogenic; and Foldetta (combining FoldX‑MD and Rosetta outputs) also predicts Pathogenic. No prediction or folding stability result is missing or inconclusive. Based on the collective evidence, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because no ClinVar classification exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	PH	0.254060	Structured	0.426845	Uncertain	0.903	0.279	0.000							-15.727	Likely Pathogenic	1.000	Likely Pathogenic	Likely Pathogenic	0.904	Likely Pathogenic	0.1381	0.1837		3.00	Destabilizing	1.5	2.20	Destabilizing	2.60	Destabilizing	1.33	Destabilizing	-9.90	Deleterious	0.969	Probably Damaging	0.680	Possibly Damaging	5.80	Benign	0.00	Affected			-4	-3	-7.0	53.05
c.1004G>T	R335L 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant R335L is not listed in ClinVar (ClinVar ID None) and has no reported allele in gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, Rosetta, Foldetta, and premPS. Tools that agree on a pathogenic effect include SGM‑Consensus (Likely Pathogenic), PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. AlphaMissense‑Optimized and FoldX are uncertain and are treated as unavailable for pathogenicity inference. High‑accuracy assessments: AlphaMissense‑Optimized is uncertain; the SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, predicts pathogenic; Foldetta, which integrates FoldX‑MD and Rosetta outputs, predicts benign. Overall, the majority of predictions (8 pathogenic vs. 4 benign) indicate that the variant is most likely pathogenic. This conclusion does not contradict ClinVar status, as no ClinVar assertion is present. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.305330	Structured	0.331028	Uncertain	0.483	0.428	0.500							-13.226	Likely Pathogenic	0.938	Likely Pathogenic	Ambiguous	0.196	Likely Benign	0.1382	0.4753		0.51	Ambiguous	0.0	-0.19	Likely Benign	0.16	Likely Benign	0.40	Likely Benign	-4.77	Deleterious	0.999	Probably Damaging	0.997	Probably Damaging	1.73	Pathogenic	0.04	Affected			-3	-2	8.3	-43.03
c.2579T>A	V860D 2D AIThe SynGAP1 missense variant V860D is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (Likely Benign). Tools that predict a pathogenic outcome are polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and AlphaMissense‑Default. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are not available. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.545602	Disordered	0.518121	Binding	0.269	0.803	0.250							-4.310	Likely Benign	0.590	Likely Pathogenic	Likely Benign	0.164	Likely Benign	0.1382	0.1047											-1.98	Neutral	0.971	Probably Damaging	0.690	Possibly Damaging	4.08	Benign	0.00	Affected			-2	-3	-7.7	15.96
c.3986T>A	L1329Q 2D AIThe SynGAP1 missense variant L1329Q is reported in gnomAD (ID 6‑33451860‑T‑A) but has no ClinVar entry. Functional prediction tools cluster into two groups: benign predictions come from REVEL, ESM1b, and FATHMM, whereas pathogenic predictions are made by PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized classifying the variant as pathogenic; the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive, and Foldetta stability analysis is unavailable. Overall, the majority of evidence points to a deleterious effect, indicating that the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.930790	Disordered	0.924905	Binding	0.336	0.748	0.875				6-33451860-T-A			-4.106	Likely Benign	0.956	Likely Pathogenic	Likely Pathogenic	0.157	Likely Benign	0.1382	0.1505											-3.31	Deleterious	0.994	Probably Damaging	0.993	Probably Damaging	3.05	Benign	0.00	Affected	3.77	5	-2	-2	-7.3	14.97
c.10T>A	S4T 2D AIThe SynGAP1 missense variant S4T is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome. The high‑accuracy consensus, SGM‑Consensus, is derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, all of which are benign, and therefore SGM‑Consensus also predicts benign. AlphaMissense‑Optimized independently predicts benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the preponderance of evidence from both general and high‑accuracy tools indicates that the variant is most likely benign, and this assessment does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.608892	Disordered	0.547364	Binding	0.390	0.924	0.750							-4.598	Likely Benign	0.130	Likely Benign	Likely Benign	0.041	Likely Benign	0.1383	0.6572											-0.01	Neutral	0.140	Benign	0.153	Benign	4.18	Benign	0.00	Affected			1	1	0.1	14.03
c.1426T>A	F476I 2D 3DClick to see structure in 3D Viewer AISynGAP1 missense variant F476I has no ClinVar entry and is not reported in gnomAD. Functional prediction tools fall into two groups: benign predictions come from REVEL, premPS, PROVEAN, SIFT, and FATHMM; pathogenic predictions come from FoldX, Rosetta, polyPhen‑2 (HumDiv and HumVar), ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic, while the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—remains inconclusive and is treated as unavailable. With seven tools indicating pathogenicity versus five indicating benign, and two high‑accuracy tools supporting pathogenicity, the evidence points to a likely pathogenic effect. This conclusion is not contradicted by ClinVar, which contains no record for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		GAP	0.257454	Structured	0.397815	Uncertain	0.821	0.250	0.000							-12.617	Likely Pathogenic	0.962	Likely Pathogenic	Likely Pathogenic	0.239	Likely Benign	0.1383	0.2202		3.90	Destabilizing	0.1	3.09	Destabilizing	3.50	Destabilizing	0.39	Likely Benign	-1.23	Neutral	0.997	Probably Damaging	0.989	Probably Damaging	3.50	Benign	0.37	Tolerated			1	0	1.7	-34.02
c.2107C>G	L703V 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L703V is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include SGM‑Consensus (Likely Benign), REVEL, PROVEAN, polyPhen‑2 HumVar, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are FoldX, Rosetta, Foldetta, premPS, polyPhen‑2 HumDiv, SIFT, and ESM1b. High‑accuracy assessments show AlphaMissense‑Optimized as benign, SGM‑Consensus (derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) as Likely Benign, and Foldetta (combining FoldX‑MD and Rosetta outputs) as pathogenic. Because the variant is not present in ClinVar or gnomAD, there is no existing clinical classification to contradict. Overall, the majority of predictions and the two high‑accuracy benign assessments suggest the variant is most likely benign, although the Foldetta result indicates a potential pathogenic effect that warrants further functional investigation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.144935	Structured	0.388282	Uncertain	0.929	0.353	0.000							-10.086	Likely Pathogenic	0.301	Likely Benign	Likely Benign	0.080	Likely Benign	0.1383	0.2621		2.32	Destabilizing	0.1	2.61	Destabilizing	2.47	Destabilizing	1.07	Destabilizing	-2.22	Neutral	0.789	Possibly Damaging	0.352	Benign	3.19	Benign	0.00	Affected			2	1	0.4	-14.03
c.3625C>G	L1209V 2D AIThe SynGAP1 L1209V missense change is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Functional prediction tools cluster into two groups: benign predictions come from REVEL and PROVEAN, while pathogenic predictions arise from polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Uncertain, SGM‑Consensus as Likely Pathogenic, and Foldetta results are unavailable. Taken together, the majority of evidence points toward a pathogenic effect, and this conclusion does not contradict the ClinVar status, which currently contains no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.583711	Binding	0.899	0.574	0.375							-9.962	Likely Pathogenic	0.953	Likely Pathogenic	Ambiguous	0.152	Likely Benign	0.1383	0.2289											-2.39	Neutral	0.999	Probably Damaging	0.994	Probably Damaging	1.54	Pathogenic	0.00	Affected			2	1	0.4	-14.03
c.1205T>A	L402Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant L402Q is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are limited to FATHMM, whereas the remaining 13 tools (SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized) uniformly predict a pathogenic impact. High‑accuracy methods reinforce this view: AlphaMissense‑Optimized scores the variant as pathogenic; the SGM Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, labels it Likely Pathogenic; and Foldetta, which integrates FoldX‑MD and Rosetta stability calculations, also predicts pathogenicity. No prediction or stability result is missing or inconclusive. Consequently, the variant is most likely pathogenic based on the collective computational evidence, and this assessment does not contradict any ClinVar annotation because none exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	C2	0.243554	Structured	0.431978	Uncertain	0.961	0.383	0.000							-13.403	Likely Pathogenic	0.996	Likely Pathogenic	Likely Pathogenic	0.523	Likely Pathogenic	0.1384	0.1173		2.93	Destabilizing	0.0	2.55	Destabilizing	2.74	Destabilizing	2.09	Destabilizing	-4.52	Deleterious	0.999	Probably Damaging	0.957	Probably Damaging	3.69	Benign	0.00	Affected			-2	-2	-7.3	14.97
c.2613C>A	H871Q 2D AIThe SynGAP1 missense variant H871Q is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized predicts benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) reports a likely benign outcome. Foldetta results are unavailable. Overall, the collective evidence strongly supports a benign classification, and this conclusion is consistent with the lack of a ClinVar entry, so there is no contradiction with existing clinical annotations. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.480142	Structured	0.679301	Binding	0.279	0.858	0.250							-4.049	Likely Benign	0.140	Likely Benign	Likely Benign	0.061	Likely Benign	0.1384	0.3357											-0.67	Neutral	0.255	Benign	0.113	Benign	2.69	Benign	0.17	Tolerated	3.88	3	0	3	-0.3	-9.01
c.2613C>G	H871Q 2D AIThe SynGAP1 missense variant H871Q is reported in gnomAD (ID 6‑33443165‑C‑G) and has no ClinVar entry. Functional prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the substitution as benign. No tool predicts pathogenicity. The high‑accuracy consensus methods corroborate this: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is “Likely Benign.” Foldetta, a protein‑folding stability predictor, was not available for this variant. Overall, the evidence strongly supports a benign impact. This conclusion is consistent with the absence of a ClinVar pathogenic classification, so there is no contradiction with ClinVar status. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.480142	Structured	0.679301	Binding	0.279	0.858	0.250				6-33443165-C-G	1	6.20e-7	-4.049	Likely Benign	0.140	Likely Benign	Likely Benign	0.061	Likely Benign	0.1384	0.3357											-0.67	Neutral	0.255	Benign	0.113	Benign	2.69	Benign	0.17	Tolerated	3.88	3	0	3	-0.3	-9.01
c.3220C>G	Q1074E 2D AIThe SynGAP1 missense variant Q1074E is not reported in ClinVar and is absent from gnomAD. Functional prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. No tool predicts a pathogenic outcome; AlphaMissense‑Default is uncertain. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, classifies the variant as Likely Benign. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus (majority vote) also indicates benign. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of available predictions strongly suggests that the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.930790	Disordered	0.987006	Binding	0.339	0.897	0.750							-2.815	Likely Benign	0.419	Ambiguous	Likely Benign	0.096	Likely Benign	0.1386	0.2856											-0.79	Neutral	0.264	Benign	0.103	Benign	2.79	Benign	0.24	Tolerated			2	2	0.0	0.98
c.3401C>A	T1134N 2D AIThe SynGAP1 missense variant T1134N is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only SIFT predicts a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is likely benign; Foldetta results are not available. Overall, the preponderance of evidence indicates that T1134N is most likely benign, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.885302	Disordered	0.813034	Binding	0.335	0.885	0.875							-4.368	Likely Benign	0.176	Likely Benign	Likely Benign	0.193	Likely Benign	0.1386	0.4870											-0.34	Neutral	0.001	Benign	0.001	Benign	5.42	Benign	0.04	Affected			0	0	-2.8	13.00
c.3538C>G	L1180V 2D AIThe SynGAP1 missense variant L1180V is not reported in ClinVar and is absent from gnomAD. Functional prediction tools show a split: benign calls from REVEL, PROVEAN, ESM1b, FATHMM, and AlphaMissense‑Optimized, whereas pathogenic calls come from polyPhen‑2 (HumDiv and HumVar), SIFT, and AlphaMissense‑Default. Grouping by consensus, the majority of tools (five) predict benign, while four predict pathogenic. The high‑accuracy consensus, SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also indicates a likely benign outcome. AlphaMissense‑Optimized independently predicts benign. No Foldetta stability assessment is available. Overall, the preponderance of evidence points to a benign effect for the variant, and this conclusion does not conflict with the absence of a ClinVar classification. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	Coiled-coil	0.626927	Disordered	0.559845	Binding	0.591	0.672	0.250							-4.664	Likely Benign	0.741	Likely Pathogenic	Likely Benign	0.086	Likely Benign	0.1386	0.1991											-1.00	Neutral	0.856	Possibly Damaging	0.474	Possibly Damaging	2.71	Benign	0.00	Affected			2	1	0.4	-14.03
c.3979C>A	P1327T 2D AIThe SynGAP1 missense variant P1327T is reported in gnomAD (ID 6‑33451853‑C‑A) but has no ClinVar entry. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. Only the two polyPhen‑2 implementations (HumDiv and HumVar) predict a pathogenic outcome. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, yields a “Likely Benign” verdict. High‑accuracy assessments reinforce this: AlphaMissense‑Optimized is benign, and the SGM‑Consensus is also benign; Foldetta results are not available. Taken together, the majority of evidence points to a benign impact. There is no ClinVar classification to contradict this conclusion. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.896620	Disordered	0.900145	Binding	0.369	0.777	0.875				6-33451853-C-A			-5.263	Likely Benign	0.150	Likely Benign	Likely Benign	0.144	Likely Benign	0.1386	0.4779											1.20	Neutral	0.994	Probably Damaging	0.908	Possibly Damaging	4.51	Benign	1.00	Tolerated	3.77	5	-1	0	0.9	3.99
c.1106C>A	T369K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant T369K is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, FoldX, premPS, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are FATHMM and AlphaMissense‑Default. Foldetta and Rosetta give uncertain results, which are treated as unavailable. High‑accuracy assessments show AlphaMissense‑Optimized as benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is inconclusive (two benign vs two pathogenic). Foldetta’s stability prediction is uncertain. Overall, the majority of evidence (nine benign vs two pathogenic) supports a benign classification. This conclusion does not contradict ClinVar status, as no ClinVar assertion exists for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		C2	0.468512	Structured	0.437011	Uncertain	0.417	0.707	0.500							-5.884	Likely Benign	0.616	Likely Pathogenic	Likely Benign	0.102	Likely Benign	0.1387	0.3855		-0.10	Likely Benign	0.1	1.13	Ambiguous	0.52	Ambiguous	0.27	Likely Benign	-1.87	Neutral	0.118	Benign	0.054	Benign	1.84	Pathogenic	0.34	Tolerated			0	-1	-3.2	27.07
c.3311C>G	P1104R 2D AIThe SynGAP1 missense variant P1104R is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and polyPhen‑2 HumVar. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as Likely Benign. High‑accuracy assessments further support a benign classification: AlphaMissense‑Optimized predicts Benign, and the SGM‑Consensus likewise indicates Likely Benign. No Foldetta stability analysis is available for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.936162	Disordered	0.954801	Binding	0.440	0.863	0.875							-3.864	Likely Benign	0.328	Likely Benign	Likely Benign	0.099	Likely Benign	0.1387	0.3703											-0.64	Neutral	0.986	Probably Damaging	0.761	Possibly Damaging	2.68	Benign	0.06	Tolerated			0	-2	-2.9	59.07
c.83C>G	S28C 2D AIThe SynGAP1 missense variant S28C is not reported in ClinVar and is absent from gnomAD. In silico prediction tools uniformly indicate a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also reports a likely benign outcome. No pathogenic predictions are present among the evaluated tools. High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates likely benign; Foldetta results are unavailable. Consequently, the variant is most likely benign based on the collective predictions, and this assessment does not contradict any ClinVar status, as no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.545602	Disordered	0.438157	Uncertain	0.354	0.884	0.125							-4.800	Likely Benign	0.107	Likely Benign	Likely Benign	0.021	Likely Benign	0.1387	0.5741											-0.26	Neutral	0.022	Benign	0.004	Benign	4.13	Benign	0.11	Tolerated			0	-1	3.3	16.06
c.1414G>C	E472Q 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant E472Q is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include only Foldetta, which classifies the variant as benign. Tools that predict a pathogenic effect are REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN). Uncertain or inconclusive predictions come from FoldX, Rosetta, and premPS. High‑accuracy assessments show AlphaMissense‑Optimized as pathogenic, SGM‑Consensus as likely pathogenic, and Foldetta as benign. Overall, the majority of evidence points to a pathogenic impact for E472Q, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.264545	Structured	0.359300	Uncertain	0.878	0.231	0.000							-13.760	Likely Pathogenic	0.984	Likely Pathogenic	Likely Pathogenic	0.555	Likely Pathogenic	0.1388	0.5726		1.34	Ambiguous	0.3	-0.67	Ambiguous	0.34	Likely Benign	0.89	Ambiguous	-2.95	Deleterious	0.994	Probably Damaging	0.986	Probably Damaging	2.39	Pathogenic	0.01	Affected			2	2	0.0	-0.98
c.2911C>A	P971T 2D AIThe SynGAP1 missense variant P971T is not reported in ClinVar and is absent from gnomAD. Functional prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while the single pathogenic prediction comes from SIFT. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus also indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta, has no available result for this variant. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.950334	Disordered	0.951523	Binding	0.545	0.905	0.625							-5.627	Likely Benign	0.053	Likely Benign	Likely Benign	0.053	Likely Benign	0.1388	0.5888											-0.95	Neutral	0.001	Benign	0.003	Benign	3.96	Benign	0.00	Affected			0	-1	0.9	3.99
c.3332A>T	K1111M 2D AIThe SynGAP1 missense variant K1111M is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Optimized, and the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN). Only AlphaMissense‑Default predicts a pathogenic outcome. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; the Foldetta protein‑folding stability analysis is unavailable. Taken together, the majority of evidence points to a benign impact for K1111M. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.910643	Disordered	0.921455	Binding	0.300	0.902	0.875							-5.579	Likely Benign	0.759	Likely Pathogenic	Likely Benign	0.071	Likely Benign	0.1388	0.4701											-1.75	Neutral	0.072	Benign	0.029	Benign	2.59	Benign	0.12	Tolerated			0	-1	5.8	3.02
c.3613C>G	L1205V 2D AIThe SynGAP1 missense variant L1205V is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include only REVEL, whereas the remaining tools—PROVEAN, polyPhen‑2 (HumDiv and HumVar), SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized—consistently predict a pathogenic impact. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, also classifies the variant as Likely Pathogenic. High‑accuracy assessments show AlphaMissense‑Optimized as Pathogenic and the SGM‑Consensus as Likely Pathogenic; Foldetta results are unavailable. Based on the preponderance of pathogenic predictions and the lack of benign consensus, the variant is most likely pathogenic, and this assessment does not contradict any ClinVar status (none is available). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	Coiled-coil	0.595080	Disordered	0.552471	Binding	0.880	0.576	0.375							-12.077	Likely Pathogenic	0.986	Likely Pathogenic	Likely Pathogenic	0.194	Likely Benign	0.1388	0.2289											-2.59	Deleterious	0.999	Probably Damaging	0.994	Probably Damaging	1.54	Pathogenic	0.00	Affected			2	1	0.4	-14.03
c.1979T>A	M660K 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant M660K is not reported in ClinVar and is absent from gnomAD. Prediction tools that agree on a benign effect are polyPhen‑2 HumVar and FATHMM. All other evaluated predictors—SGM‑Consensus, REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, SIFT, ESM1b, AlphaMissense‑Default, and AlphaMissense‑Optimized—classify the variant as pathogenic. High‑accuracy assessments further support a deleterious impact: AlphaMissense‑Optimized predicts pathogenicity; the SGM‑Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) also indicates pathogenicity; and Foldetta, which integrates FoldX‑MD and Rosetta stability outputs, reports a pathogenic effect. Based on the overwhelming consensus of pathogenic predictions and the corroborating high‑accuracy tools, the variant is most likely pathogenic, and this conclusion does not contradict the current ClinVar status, which has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.047319	Structured	0.134270	Uncertain	0.944	0.289	0.000							-14.123	Likely Pathogenic	0.995	Likely Pathogenic	Likely Pathogenic	0.604	Likely Pathogenic	0.1389	0.0856		3.13	Destabilizing	0.1	4.46	Destabilizing	3.80	Destabilizing	2.36	Destabilizing	-5.99	Deleterious	0.862	Possibly Damaging	0.216	Benign	3.34	Benign	0.00	Affected			0	-1	-5.8	-3.02
c.2144C>G	P715R 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant P715R is not reported in ClinVar and is absent from gnomAD. Prediction tools that indicate a benign effect include REVEL and FATHMM, whereas the majority of other in silico predictors (SGM‑Consensus, FoldX, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default) classify the change as pathogenic. High‑accuracy assessments show that the SGM‑Consensus (a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) predicts a likely pathogenic outcome, AlphaMissense‑Optimized is inconclusive, and Foldetta (combining FoldX‑MD and Rosetta outputs) is also inconclusive. Because the pathogenic predictions outnumber the benign ones and the high‑accuracy consensus supports a deleterious effect, the variant is most likely pathogenic. This assessment does not contradict ClinVar, which currently has no entry for this variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic	GAP	0.243554	Structured	0.409757	Uncertain	0.956	0.362	0.000							-12.191	Likely Pathogenic	0.940	Likely Pathogenic	Ambiguous	0.324	Likely Benign	0.1389	0.2620		2.19	Destabilizing	0.1	0.53	Ambiguous	1.36	Ambiguous	0.87	Ambiguous	-8.09	Deleterious	1.000	Probably Damaging	0.998	Probably Damaging	3.53	Benign	0.01	Affected			0	-2	-2.9	59.07
c.2784G>C	Q928H 2D AIThe SynGAP1 missense variant Q928H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include REVEL and ESM1b, whereas the majority of tools predict it to be pathogenic: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—agrees on a pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.986260	Binding	0.324	0.852	0.250							-4.358	Likely Benign	0.929	Likely Pathogenic	Ambiguous	0.329	Likely Benign	0.1389	0.4811											-3.65	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.54	Pathogenic	0.00	Affected			3	0	0.3	9.01
c.2784G>T	Q928H 2D AIThe SynGAP1 missense variant Q928H is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that classify the variant as benign include REVEL and ESM1b, whereas the majority of tools predict it to be pathogenic: PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, FATHMM, and AlphaMissense‑Default. High‑accuracy assessments further support a pathogenic interpretation: AlphaMissense‑Optimized is uncertain, but the SGM Consensus—derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—agrees on a pathogenic outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, was not available for this variant. Overall, the preponderance of evidence indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because no ClinVar entry exists. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Pathogenic		0.497853	Structured	0.986260	Binding	0.324	0.852	0.250							-4.358	Likely Benign	0.929	Likely Pathogenic	Ambiguous	0.330	Likely Benign	0.1389	0.4811											-3.65	Deleterious	0.998	Probably Damaging	0.996	Probably Damaging	1.54	Pathogenic	0.00	Affected			3	0	0.3	9.01
c.1604G>A	S535N 2D 3DClick to see structure in 3D Viewer AIThe SynGAP1 missense variant S535N is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD. Across the broad panel of in‑silico predictors, 13 tools (REVEL, FoldX, Rosetta, Foldetta, premPS, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, ESM1b, AlphaMissense‑Default, AlphaMissense‑Optimized, and the SGM‑Consensus “Likely Benign”) uniformly predict a benign effect, whereas only FATHMM assigns a pathogenic label. High‑accuracy assessments corroborate the benign consensus: AlphaMissense‑Optimized is benign, the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) is “Likely Benign,” and Foldetta (combining FoldX‑MD and Rosetta outputs) predicts benign stability. Thus, the variant is most likely benign based on the available predictions, and this assessment does not contradict any ClinVar status (none reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign	GAP	0.236433	Structured	0.041365	Uncertain	0.918	0.343	0.000							-4.957	Likely Benign	0.196	Likely Benign	Likely Benign	0.176	Likely Benign	0.1390	0.4784		-0.46	Likely Benign	0.2	-0.26	Likely Benign	-0.36	Likely Benign	0.18	Likely Benign	-0.05	Neutral	0.070	Benign	0.032	Benign	-1.25	Pathogenic	0.29	Tolerated			1	1	-2.7	27.03
c.2252C>G	P751R 2D AIThe SynGAP1 missense variant P751R is catalogued in gnomAD (ID 6‑33441717‑C‑G) but has no ClinVar entry. Functional prediction tools that agree on a benign effect include REVEL, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic outcome are PROVEAN and polyPhen‑2 HumDiv. The SGM‑Consensus, derived from a majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a likely benign classification. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized predicts benign, SGM‑Consensus is likely benign, and Foldetta (a protein‑folding stability method combining FoldX‑MD and Rosetta outputs) has no available result for this variant. Based on the collective predictions, the variant is most likely benign, and this assessment does not contradict any ClinVar status (none is reported). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.618285	Disordered	0.667683	Binding	0.386	0.866	0.625				6-33441717-C-G	1	6.20e-7	-5.646	Likely Benign	0.296	Likely Benign	Likely Benign	0.157	Likely Benign	0.1390	0.3644											-2.61	Deleterious	0.719	Possibly Damaging	0.295	Benign	2.68	Benign	0.06	Tolerated	3.99	5	-2	0	-2.9	59.07
c.2723A>G	Q908R 2D AIThe SynGAP1 missense variant Q908R is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized, while polyPhen‑2 (both HumDiv and HumVar) predict a pathogenic outcome. AlphaMissense‑Default is uncertain, and the SGM‑Consensus (majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) indicates a likely benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as benign and the SGM‑Consensus as likely benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion does not contradict any ClinVar status because none is available. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.608892	Disordered	0.678728	Binding	0.275	0.917	0.250							-4.284	Likely Benign	0.485	Ambiguous	Likely Benign	0.170	Likely Benign	0.1391	0.1743											-1.02	Neutral	0.985	Probably Damaging	0.982	Probably Damaging	2.75	Benign	0.10	Tolerated			1	1	-1.0	28.06
c.3073C>G	Q1025E 2D AIThe SynGAP1 missense variant Q1025E is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only polyPhen‑2 HumDiv predicts it as pathogenic. The SGM‑Consensus, which aggregates the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports the variant as “Likely Benign.” High‑accuracy assessments confirm this view: AlphaMissense‑Optimized predicts benign, and the SGM‑Consensus likewise indicates a benign outcome. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the consensus of available predictions indicates that the variant is most likely benign, and this conclusion does not contradict any ClinVar annotation (none is present). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.879233	Disordered	0.993410	Binding	0.363	0.746	0.500							-3.010	Likely Benign	0.254	Likely Benign	Likely Benign	0.077	Likely Benign	0.1391	0.2269											-0.60	Neutral	0.649	Possibly Damaging	0.353	Benign	2.79	Benign	1.00	Tolerated			2	2	0.0	0.98
c.2727G>A	M909I 2D AIThe SynGAP1 missense variant M909I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; the Foldetta protein‑folding stability analysis is unavailable. Overall, the majority of evidence points to a benign impact, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.642678	Disordered	0.696196	Binding	0.314	0.914	0.250							-3.636	Likely Benign	0.703	Likely Pathogenic	Likely Benign	0.097	Likely Benign	0.1392	0.3298											-1.15	Neutral	0.481	Possibly Damaging	0.220	Benign	2.82	Benign	0.25	Tolerated			2	1	2.6	-18.03
c.2727G>C	M909I 2D AIThe SynGAP1 missense variant M909I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.642678	Disordered	0.696196	Binding	0.314	0.914	0.250							-3.636	Likely Benign	0.703	Likely Pathogenic	Likely Benign	0.097	Likely Benign	0.1392	0.3298											-1.15	Neutral	0.481	Possibly Damaging	0.220	Benign	2.82	Benign	0.25	Tolerated			2	1	2.6	-18.03
c.2727G>T	M909I 2D AIThe SynGAP1 missense variant M909I is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumVar, SIFT, ESM1b, FATHMM, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are polyPhen‑2 HumDiv and AlphaMissense‑Default. The SGM‑Consensus, which aggregates AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN, reports a Likely Benign classification. High‑accuracy assessments show AlphaMissense‑Optimized as Benign and the SGM‑Consensus as Likely Benign; Foldetta results are unavailable. Overall, the majority of evidence points to a benign impact. This conclusion is consistent with the lack of ClinVar annotation, so there is no contradiction with existing clinical data. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.642678	Disordered	0.696196	Binding	0.314	0.914	0.250							-3.636	Likely Benign	0.703	Likely Pathogenic	Likely Benign	0.097	Likely Benign	0.1392	0.3298											-1.15	Neutral	0.481	Possibly Damaging	0.220	Benign	2.82	Benign	0.25	Tolerated			2	1	2.6	-18.03
c.2849G>T	G950V 2D AIThe SynGAP1 missense variant G950V is not reported in ClinVar (ClinVar ID: None) and is absent from gnomAD (gnomAD ID: None). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, AlphaMissense‑Default, and AlphaMissense‑Optimized. Tools that predict a pathogenic effect are SIFT and FATHMM, while ESM1b remains uncertain. High‑accuracy assessments further support a benign interpretation: AlphaMissense‑Optimized is benign, and the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) also yields a benign prediction. Foldetta, a protein‑folding stability method, has no available result for this variant. Overall, the preponderance of evidence indicates that G950V is most likely benign, and this conclusion does not contradict the ClinVar status, which currently has no entry for the variant. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.987317	Disordered	0.888649	Binding	0.368	0.923	0.750							-7.796	In-Between	0.093	Likely Benign	Likely Benign	0.428	Likely Benign	0.1392	0.3507											-0.91	Neutral	0.411	Benign	0.239	Benign	2.26	Pathogenic	0.01	Affected			-1	-3	4.6	42.08
c.2918G>T	G973V 2D AIThe SynGAP1 missense variant G973V is not reported in ClinVar and is absent from gnomAD. Prediction tools largely agree on a benign effect: REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), ESM1b, FATHMM, AlphaMissense‑Default, and AlphaMissense‑Optimized all classify the change as benign, while only SIFT predicts it as pathogenic. Grouping by consensus, the benign‑predicting tools outnumber the single pathogenic prediction. High‑accuracy assessments reinforce this view: AlphaMissense‑Optimized reports a benign outcome, and the SGM Consensus—derived from the majority vote of AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN—also yields a benign classification. Foldetta results are unavailable, so they do not influence the assessment. Overall, the variant is most likely benign, and this conclusion is not contradicted by any ClinVar annotation. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.	Likely Benign		0.887230	Disordered	0.959498	Binding	0.390	0.897	0.625							-4.688	Likely Benign	0.097	Likely Benign	Likely Benign	0.092	Likely Benign	0.1392	0.3684											-0.76	Neutral	0.224	Benign	0.091	Benign	4.18	Benign	0.01	Affected			-1	-3	4.6	42.08
c.3799A>C	M1267L 2D AIThe SynGAP1 missense variant M1267L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta results are unavailable. Overall, the majority of evidence (five pathogenic‑predicting tools versus three benign) indicates that the variant is most likely pathogenic, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.429200	Structured	0.812047	Binding	0.847	0.614	0.000							-1.766	Likely Benign	0.399	Ambiguous	Likely Benign	0.293	Likely Benign	0.1392	0.3626											-2.52	Deleterious	0.813	Possibly Damaging	0.456	Possibly Damaging	2.36	Pathogenic	0.00	Affected			4	2	1.9	-18.03
c.3799A>T	M1267L 2D AIThe SynGAP1 missense variant M1267L is not reported in ClinVar (ClinVar ID None) and is absent from gnomAD (gnomAD ID None). Prediction tools that agree on a benign effect include REVEL, ESM1b, and AlphaMissense‑Optimized. Tools that agree on a pathogenic effect are PROVEAN, polyPhen‑2 HumDiv, polyPhen‑2 HumVar, SIFT, and FATHMM. AlphaMissense‑Default is uncertain. High‑accuracy assessments show AlphaMissense‑Optimized predicts benign, while the SGM Consensus (majority vote from AlphaMissense‑Default, ESM1b, FATHMM, PROVEAN) predicts pathogenic. Foldetta, a protein‑folding stability method combining FoldX‑MD and Rosetta outputs, has no available result for this variant. Overall, the majority of evidence (five pathogenic‑predicting tools versus three benign‑predicting tools) indicates that M1267L is most likely pathogenic, and this conclusion does not contradict any ClinVar status because the variant is not yet catalogued there. Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.		Coiled-coil	0.429200	Structured	0.812047	Binding	0.847	0.614	0.000							-1.766	Likely Benign	0.399	Ambiguous	Likely Benign	0.293	Likely Benign	0.1392	0.3626											-2.52	Deleterious	0.813	Possibly Damaging	0.456	Possibly Damaging	2.36	Pathogenic	0.00	Affected			4	2	1.9	-18.03
c.501C>A	D167E 2D AIThe SynGAP1 D167E missense variant is not reported in ClinVar (no ClinVar ID) and is absent from gnomAD (no gnomAD ID). Prediction tools that agree on a benign effect include REVEL, PROVEAN, polyPhen‑2 (HumDiv and HumVar), FATHMM, and AlphaMissense‑Optimized. Only SIFT predicts a pathogenic outcome, while ESM1b and AlphaMissense‑Default are uncertain. High‑accuracy assessments show AlphaMissense‑Optimized as benign; the SGM Consensus (derived from AlphaMissense‑Default, ESM1b, FATHMM, and PROVEAN) is inconclusive because it receives two benign votes and two uncertain votes, yielding no clear majority. Foldetta, which would provide a protein‑folding stability estimate, has no available result for this variant. Overall, the preponderance of evidence points to a benign impact, and this conclusion does not contradict any ClinVar annotation (none exists). Disclaimer: This summary was generated using AI and should be interpreted alongside expert review.			0.429200	Structured	0.502306	Binding	0.377	0.667	0.375							-7.636	In-Between	0.516	Ambiguous	Likely Benign	0.067	Likely Benign	0.1392	0.7144											-1.52	Neutral	0.063	Benign	0.062	Benign	4.07	Benign	0.00	Affected			3	2	0.0	14.03